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Mechanism of Huatan Sanjie Fang in improving goiter in Graves'disease mice based on the Hippo signaling pathway 认领 引用 被引量：1
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作者 Huimin Yuan Wenxin Ma +5 位作者 Yifei Song Hang Wang Shuxin Yan Silan Hao Xiaoyun Zhu Yang Tang 《Journal of Traditional Chinese Medical Sciences》 CAS 2023年第3期289-295,共7页
Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by i... Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway. 展开更多
关键词 Graves'disease Huatan Sanjie Fang Goiter Hippo signaling pathway Organ size Graves'disease model methimazole YAP
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Research progress of the Hippo signaling pathway in renal cell carcinoma 认领 引用
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作者 Yiren Yang Xinxin Gan +4 位作者 Wei Zhang Baohua Zhu Zhao Huangfu Xiaolei Shi Linhui Wang 《Asian Journal of Urology》 CSCD 2024年第4期511-520,共10页
Objective:This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hi... Objective:This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hippo signaling pathway, which regulates tissue and organ sizes, plays a crucial role in RCC progression and metastasis. Understanding the involvement of the Hippo signaling pathway in RCC provides valuable insights for the development of targeted therapies and improved patient outcomes.Methods:In this review, we explored the impact of the Hippo signaling pathway on RCC. Through an analysis of existing literature, we examined its role in RCC progression and metastasis. Additionally, we discussed potential therapeutic strategies targeting the Hippo pathway for inhibiting RCC cell growth and invasion. We also highlighted the importance of investigating interactions between the Hippo pathway and other signaling pathways such as Wnt, transforming growth factor-beta, and PI3K/AKT, which may uncover additional therapeutic targets.Results:The Hippo signaling pathway has shown promise as a target for inhibiting RCC cell growth and invasion. Studies have demonstrated its dysregulation in RCC, with altered expression of key components such as yes-associated proteinranscriptional coactivator with PDZ-binding motif (YAP/TAZ). Targeting the Hippo pathway has been associated with suppressed tumor growth and metastasis in preclinical models of RCC. Furthermore, investigating crosstalk between the Hippo pathway and other signaling pathways has revealed potential synergistic effects that could be exploited for therapeutic interventions.Conclusion:Understanding the role of the Hippo signaling pathway in RCC is of paramount importance. Elucidating its functions and molecular interactions contributes to RCC diagnosis, treatment, and the discovery of novel mechanisms. This knowledge informs the development of innovative therapeutic strategies and opens new avenues for research in RCC. Further investigations are warranted to fully comprehend the complex interplay between the Hippo pathway and other signaling pathways, ultimately leading to improved outcomes for RCC patients. 展开更多
关键词 The Hippo signaling pathway YAP/TAZ Renal cell carcinoma Proliferation Metastasis Prognosis
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Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway 认领 引用 被引量：1
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作者 Xiaomin Li Qing Liu +2 位作者 Songyu Xie Xiaoping Wu Junsheng Fu 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第2期1040-1054,共15页
Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in ... Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma. 展开更多
关键词 Cordycepin Hepatocellular carcinoma Hippo signaling pathway GBP3 ETV5
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Scutellarin induces apoptosis of colorectal cancer HCT116 cells via Hippo signaling pathway 认领 引用
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作者 YANG Han SUN Qiang +7 位作者 ZENG Sha CHEN Li ZHAO Hui LIU Mao-lun REN Shan MING Tian-qi LU Jin-jian XU Hai-bo 《中国药理学与毒理学杂志》 CAS 北大核心 2021年第10期775-776,共2页
OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro.METHODS MTT colorimetric method was used to detect the influence of scutell... OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro.METHODS MTT colorimetric method was used to detect the influence of scutellarin on the survival rate of HCT116 cells.And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy.Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells.Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells.Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,p-YAP(Ser127),TAZ,and its downstream effector proteins c-Myc and cyclin D1,as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells.RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells.Hoechst33342/PI double staining showed that scutellarin effectively induced the apoptosis of HCT116 cells.Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,TAZ and its downstream effector proteins c-Myc,cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin,and the expression of p-YAP(ser127)was up-regulated.Moreover,scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2,and promoted the protein level of Bax.CONCLUSION Scutellarin may inhibit the proliferation and migration of HCT116 cells,while induce its apoptosis,potentially by activation of Hippo signaling pathway. 展开更多
关键词 scutellarin colorectal cancer HCT116 cells Hippo signaling pathway
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circTP63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway 认领 引用 被引量：5
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作者 Dan Wang Sicheng Zuo +15 位作者 Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo 《Science China(Life Sciences)》 SCIE CAS CSCD 2025年第3期689-705,共17页
Circular RNAs(circRNAs)play pivotal roles in the development and progression of various diseases,including malignant tumors.However,the biological functions and the underlying mechanisms of many circRNAs remain elusiv... Circular RNAs(circRNAs)play pivotal roles in the development and progression of various diseases,including malignant tumors.However,the biological functions and the underlying mechanisms of many circRNAs remain elusive.In this study,we identified a novel circRNA,circTP63-N,generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC).circTP63-N was found to be downregulated in clinical samples of NPC.Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells.Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein,leading to the recruitment of LATS/YAP1 proteins.This,in turn,induced phosphorylation and ubiquitination-dependent degradation of YAP1,resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes,including INHBA,MMP3,and CCNE2.Our findings highlight the identification of circTP63-N,a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC.These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC. 展开更多
关键词 nasopharyngeal carcinoma circTP63-N HSP90AB1 YAP1/Hippo signaling pathway proliferation metastasis
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Pleurotus pulmonarius polysaccharides inhibit glioma growth through the Hippo signaling pathway and regulate the structure of gut microbiota 认领 引用 被引量：2
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作者 Jing Chen Yong Peng +4 位作者 Bing-Bo Zhuang Shuang Liu Chun-Hua Wang Guo-Liang Zhang Ri-Sheng Liang 《Food Bioscience》 SCIE 2024年第3期3791-3802,共12页
Pleurotus pulmonarius(Fr.)is an edible and medicinal fungus.Here,we isolated polysaccharides from P.pulmonarius and evaluated their physicochemical properties,anti-tumor activity,and gut microbiota regula-tion.Freeze-... Pleurotus pulmonarius(Fr.)is an edible and medicinal fungus.Here,we isolated polysaccharides from P.pulmonarius and evaluated their physicochemical properties,anti-tumor activity,and gut microbiota regula-tion.Freeze-dried powder of P.pulmonarius fruiting body polysaccharide(PFP)is a heteropolysaccharide,mainly composed of galactose(295.52μg/mg).PFP significantly inhibited glioma cell survival in vitro and U251 glioma cell tumor growth in nude mice(inhibition rate,53.70%).PFP inhibited YAP1 and TAZ protein expression levels,upregulated those of MST1 and LAST1,regulated Hippo signaling,stimulated E-cadherin,and downregulated N-cadherin proteins,inhibiting tumor migration.PFP downregulated Bcl-2 protein expression,upregulated that of Cleaved Caspase 3,and induced tumor cell apoptosis.PFP regulated gut microbiota structure in tumor-bearing nude mice and increased the relative abundance of beneficial bacteria.In summary,PFP is a natural,safe,and non-toxic anti-cancer drug,and a potential probiotic.Our data provide theoretical guidance for the treatment of glioma. 展开更多
关键词 PFP Pleurotus pulmonarius fruiting body polysaccharides Glioma Hippo signaling pathway Gut microbiota
Regulation of the Hippo signaling pathway by deubiquitinating enzymes in cancer 认领 引用 被引量：2
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作者 Ashley Mussell Costa Frangou Jianmin Zhang 《Genes & Diseases》 SCIE 2019年第4期335-341,共7页
Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis.The proteins that act to regulate this pathway are important for ensuring proper function and cellular location.Deu... Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis.The proteins that act to regulate this pathway are important for ensuring proper function and cellular location.Deubiquitinases(DUBs)are a family of proteases that act upon many proteins.While ubiquitinases add ubiquitin and target proteins for degradation,DUBs act by removing ubiquitin(Ub)moieties.Changes in ubiquitin chain topology results in the stabilization of proteins,membrane trafficking,and the alteration of cellular localization.While the roles of these proteins have been well established in a cancer setting,their convergence in cancer is still under investigation.In this review,we discuss the roles that DUBs play in the regulation of the Hippo signaling pathway for homeostasis and disease. 展开更多
关键词 Cancer Deubiquitinase Hippo signaling pathway Ubiquitinase YAP/TAZ
Biomolecular condensates in Hippo pathway regulation 认领 引用 被引量：1
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作者 Yangqing SHAO Yitong ZHANG +1 位作者 Wenxuan ZHU Huasong LU 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2025年第10期949-960,共12页
Hippo signaling is a highly conserved pathway central to diverse cellular processes.Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progres... Hippo signaling is a highly conserved pathway central to diverse cellular processes.Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers.Recent studies have uncovered that,in addition to the classical signaling cascade regulation,biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling.In this review,we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation,with a particular focus on transcriptional activation mediated by Yes-associated protein(YAP)ranscriptional coactivator with post-synaptic density-95,disks-large,and zonula occludens-1(PDZ)-binding domain(TAZ)condensates.Furthermore,we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma(FUS)in modulating the biophysical properties of TAZ condensates,which in turn influence their transcriptional activity and pro-tumorigenic functions.These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity. 展开更多
关键词 Hippo signaling pathway Phase separation Transcription regulation
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Dopamine receptor D1-mediated suppression of liver fibrosis via Hippo/Yes-associated protein 1 signaling in levodopa treatment 认领 引用 被引量：2
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作者 Hai-Yan Wang Man-Man Qi +2 位作者 Kai Zhang Yu-Zhao Zhu Jian Zhang 《World Journal of Gastroenterology》 SCIE CAS 2025年第34期108-118,共11页
BACKGROUND Yes-associated protein 1(YAP1),a downstream transcriptional coactivator regulated by the Hippo signaling pathway,has been shown to be involved in liver fibrosis.YAP activity is modulated by G-protein couple... BACKGROUND Yes-associated protein 1(YAP1),a downstream transcriptional coactivator regulated by the Hippo signaling pathway,has been shown to be involved in liver fibrosis.YAP activity is modulated by G-protein coupled receptors,including Gαs-coupled protein dopamine receptor D1(DRD1).Levodopa,a dopamine precursor,activates DRD1 on cell surface,triggering its downstream signaling pathway.AIM To investigate the therapeutic effect of levodopa and the downstream mechanism on carbon tetrachloride(CCl4)-induced liver fibrosis,including liver DRD1 expression.METHODS SD rats were intraperitoneally injected with 40%CCl4for 8 weeks to induce liver fibrosis,followed by treatment with varying doses of levodopa for 2 weeks.Serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were measured,and liver pathology was assessed using hematoxylin and eosin and Masson's staining.Alpha-smooth muscle actin(α-SMA)content,along with the expressions of DRD1,YAP,and phosphorylated protein,was analyzed by Western blot,immunohistochemistry,and reverse transcription-quantitative real-time polymerase chain reaction.RESULTS Compared with the controls,levodopa-treated rats showed a decrease in the proportion of collagen in the liver and a recovery from liver fibrosis(P=0.0007).Western blot and immunohistochemistry indicated that DRD1 was upregulated in the fibrotic liver of rats treated with levodopa,showing an increase in DRD1 Level(P<0.0001).In addition,the upregulation of DRD1 activated the Hippo signaling pathway,manifested as increased YAP phosphorylation(P<0.05).CONCLUSION This was the first study to demonstrate that levodopa attenuates CCl4-induced liver fibrosis by inhibiting the Hippo/YAP signaling pathways. 展开更多
关键词 Levodopa Liver fibrosis Yes1 associated transcriptional regulator Hippo/Yes-associated protein 1 signaling pathway Dopamine receptor D1
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Electroacupuncture enhances the mitophagy of granulosa cells in premature ovarian insufficiency model mice by inactivating the hippo-yes-associated protein/transcriptional co-activator with postsynaptic density protein,drosophila disc large tumor suppresso 认领 引用 被引量：1
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作者 WU Jiaman TANG Meng +4 位作者 LUO Yu ZHU Haimin ZHAO Tianqi MA Fei NING Yan 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2025年第1期13-21,共9页
OBJECTIVE:To investigate the potential mechanism of electroacupuncture(EA)in alleviating premature ovarian insufficiency(POI)and to provide a theoretical basis for EA treatment of POI.METHODS:For this purpose,a POI mi... OBJECTIVE:To investigate the potential mechanism of electroacupuncture(EA)in alleviating premature ovarian insufficiency(POI)and to provide a theoretical basis for EA treatment of POI.METHODS:For this purpose,a POI mice model was developed by injecting 12 mg/kg busulfan and 120 mg/kg cyclophosphamide intraperitoneally to induce POI.It was then proceeded by EA intervention at Guanyuan(CV4)acupoint on the second day following modeling.Similarly,apoptosis in ovarian granulosa cells was detected by terminal deoxynucleotidyl transferase d UTP nick end labeling staining,while enzyme-linked immunosorbent assay was employed for measuring serum folliclestimulating hormone(FSH),luteinizing hormone(LH),estrogen(E2),and anti-müllerian hormone(AMH)levels.Moreover,transmission electron microscopy(TEM)was employed for examining mitochondrial morphology,while autophagy and hippo-yes-associated proteinranscriptional co-activator with postsynaptic density protein,drosophila disc large tumor suppressor,and zonula occludens-1 protein binding motif(YAP/TAZ)pathway related protein levels in ovarian tissue were detected via Western blotting.RESULTS:Analysis of serum levels of various hormones indicated that serum FSH and LH were reduced in EA compared to the POI group,while E2 and AMH levels were found to be elevated in EA compared to the POI group.The EA was found to inhibit apoptosis in granulosa cells in POI model mice,in addition to improved mitochondrial damage and significantly improved mitophagy.Pathway analysis revealed that EA was involved in activating the hippo-YAP/TAZ pathway,followed by reversing EA effects on granulosa cell apoptosis and mitophagy with the use of verteporfin,an autophagy and YAP-T-cell factor/enhancer of split and activator of transcription domain family member interaction inhibitor.CONCLUSIONS:EA at the Guanyuan(CV4)acupoint protected the granulosa cell by inhibiting cell apoptosis and promoting mitophagy,which was mediated by the Hippo-YAP/TAZ pathway. 展开更多
关键词 primary ovarian insufficiency acupuncture point CV4(Guanyuan) mitophagy hippo signaling pathway
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Levodopa and the dopamine receptor D1-Hippo/yes-associated protein axis:A novel therapeutic avenue for liver fibrosis 认领 引用
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作者 Shan-Shan Xie Zhi-Gang Liu 《World Journal of Gastroenterology》 SCIE CAS 2025年第46期1-6,共6页
Liver fibrosis remains a major global health challenge with limited therapeutic options.In their recent study,Wang et al report that levodopa,a dopamine precursor widely used in Parkinson’s disease,significantly atte... Liver fibrosis remains a major global health challenge with limited therapeutic options.In their recent study,Wang et al report that levodopa,a dopamine precursor widely used in Parkinson’s disease,significantly attenuates carbon tetrachloride-induced liver fibrosis in rats by enhancing dopamine receptor D1 expression and activating the Hippo signaling pathway,leading to phosphorylation and inactivation of yes-associated protein 1.This discovery links Gprotein-coupled receptor signaling to Hippo pathway regulation in hepatic fibrosis.The work highlights the dopamine receptor D1-Hippo/yes-associated protein 1 axis as a promising antifibrotic mechanism and introduces levodopa as a potential repurposing candidate for chronic liver disease.With its established safety and affordability,levodopa offers a rapidly translatable strategy that warrants validation in human tissues and diverse fibrosis models.Here,we place these findings in the broader context of G-protein-coupled receptor regulation of hepatic stellate cell activation,discuss translational opportunities for levodopa in liver fibrosis,and propose future directions to validate this pathway across disease models and clinical settings. 展开更多
关键词 Levodopa Liver fibrosis Dopamine receptor D1 Hippo signaling pathway Yes-associated protein Drug repurposing Hepatic stellate cell G-protein coupled receptor
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PKC-eta promotes breast cancer metastasis by regulating the Hippo-YAP signaling pathway 认领 引用
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作者 Vijayasteltar B.Liju Kamran Waidha +12 位作者 Amitha Muraleedharan Divya Ram Jayaram Hodaya Haimov Sankar Jagadeeshan Dinesh Babu Manikandan Raghda Abu Shareb Livingstone Nurukurti Menachem Sklarz J.Silvio Gutkind Irit Allon Ofir Cohen Moshe Elkabets Etta Livneh 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2026年第3期1633-1652,共20页
Triple-negative breast cancer(TNBC)is an aggressive disease characterized by high metastatic potential and limited treatment options.Protein kinase C-eta(PKCη),an antiapoptotic kinase of the novel PKC subfamily,is as... Triple-negative breast cancer(TNBC)is an aggressive disease characterized by high metastatic potential and limited treatment options.Protein kinase C-eta(PKCη),an antiapoptotic kinase of the novel PKC subfamily,is associated with poor prognosis in breast cancer patients.Analysis of TNBC tumors revealed that PRKCH(PKCη)expression is linked to an epithelial‒mesenchymal transition(EMT)signature,which is indicative of a metastatic phenotype.Using genetic ablation studies,we showed that PKCηpromotes metastasis by enhancing EMT and stemness.Notably,compared with those in PKCη-intact tumors,orthotopic xenografts of PKCη-knockout cells in NSG mice resulted in reduced tumor growth and metastasis.Mechanistically,PKCηfunctions as a negative regulator of the Hippo pathway by activating YAP.PKCηphosphorylates YAP at Ser128,leading to its stabilization and nuclear translocation,which promotes metastasis.We also demonstrated that PKCηnegatively regulates AKT,thereby further sustaining the downregulation of the Hippo pathway.Finally,we show that an evolutionarily conserved peptide encoded by an upstream open reading frame(uORF)preceding the PKCηcoding sequence functions as a PKCηdegrader,activating the Hippo pathway and promoting YAP degradation.Together,our findings reveal a PKCη-driven signaling axis that regulates the Hippo-YAP pathway in TNBC metastasis,highlighting the potential therapeutic vulnerability of this aggressive disease. 展开更多
关键词 genetic ablation studieswe breast cancer PKC eta Triple negative breast cancer Epithelial mesenchymal transition antiapoptotic kinase Hippo YAP signaling pathway Metastasis
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Multidimensional Regulatory Network of YAP1 Driving Malignant Progression in Esophageal Cancer:Molecular Mechanisms and Targeted Therapy:A Review 认领 引用
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作者 Jun-Hui Chen Si-Run Du +6 位作者 Chang Liu Bei-Bei Liu Hai-Ying Xu Xin-Ying Ji Bo Feng Chun-Zheng Ma Jun-Hui Guo 《Oncology Research》 SCIE 2026年第5期267-297,共31页
Esophageal cancer(EC)ranks among the most lethal gastrointestinal malignancies.Due to challenges in early diagnosis,molecular heterogeneity,and therapeutic resistance,patient prognosis remains extremely poor,necessita... Esophageal cancer(EC)ranks among the most lethal gastrointestinal malignancies.Due to challenges in early diagnosis,molecular heterogeneity,and therapeutic resistance,patient prognosis remains extremely poor,necessitating the development of novel biomarkers and therapeutic targets.As a core effector of the Hippo signaling pathway,the potential significance of Yes-associated protein 1(YAP1)has garnered increasing attention.This paper aims to systematically summarize the multi-omics research,molecular mechanisms,and preclinicalranslational evidence for YAP1,covering its activation pathways,biological functions,clinical significance,and therapeutic strategies.We elucidated YAP1’s multidimensional regulatory network in EC,including Hippo-dependent and-independent mechanisms,cross-regulation with environmental risk factors,and its role in malignant phenotypes such as cell proliferation,apoptosis,epithelial-mesenchymal transition(EMT),and metastasis.The potential of YAP1 as a diagnostic,prognostic,and predictive biomarker is evaluated,alongside summarizing its role in mediating chemotherapy,radiotherapy,and immune tolerance mechanisms,along with recent advances in targeted therapies.This provides a theoretical foundation for subsequent basic research and precision medicine translation.As a potential hub in the EC signaling network,it is considered to play a key role in driving tumor progression and treatment resistance through multiple pathways.Targeting YAP1 holds broad clinical promise but faces challenges including functional duality,subtype heterogeneity,and complex resistance mechanisms.Future efforts should focus on developing highly selective inhibitors,integrating multi-omics technologies and innovative models to advance clinical translation and provide new strategies for precision treatment of EC patients. 展开更多
关键词 Yes-associated protein 1 esophageal cancer Hippo signaling pathway molecular mechanisms prognosis targeted therapy
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YAP1 Is a Crucial Nexus in the Tumor Microenvironment 认领 引用
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作者 Raghavan Narasimhan Anshula Narayanasamy +2 位作者 Jaya Padmanabhan Srikumar Chellappan Durairaj Mohan Kumar 《Current Medical Science》 SCIE CAS CSCD 2026年第1期1-19,共19页
Yes-associated protein-1(YAP1)is an oncogenic effector of the Hippo signaling pathway,activated in several cancer types,and has been extensively studied in cancer progression and therapy.A large number of studies have... Yes-associated protein-1(YAP1)is an oncogenic effector of the Hippo signaling pathway,activated in several cancer types,and has been extensively studied in cancer progression and therapy.A large number of studies have established the impor-tance of YAP1 in promoting cell-autonomous functions,including uncontrolled growth,sustained proliferative signaling,drug resistance,and metastasis,across multiple cancer types.Therapeutic targeting of YAP1 to combat incurable neoplasms has been the focus of intense investigations.Solid tumors exhibit an organ-like morphology that comprises malignant cells,nonmalignant cells such as fibroblasts,endothelial cells,and immune cells,and non-cellular components,including the extracellular matrix and exosomal vesicles.Tumor progression is accompanied by persistent,reciprocal interactions between malignant cells and other cell types in the tumor microenvironment(TME).Ample evidence indicates the functional importance of YAP1 in nonmalignant components of the TME,which fuel cancer progression.In this review,we provide a comprehensive overview of the functional significance of YAP1 and its downstream signaling pathways across different compartments of the TME,which orchestrate cancer growth,stemness,drug resistance,and metastasis.In particular,this review focuses on understanding the mechanisms by which YAP1 drives distinct cell types in the TME,including cancer-associated fibroblasts(CAFs),immune cells,endothelial cells,and exosome-derived factors,to fuel tumor progression.Furthermore,we summarize the progress in the development of recent YAP1 inhibitors,their mechanisms of action in Hippo-YAP1-dependent cancers,and their combination benefits with existing treatment strategies. 展开更多
关键词 Yes-associated protein 1 Tumor stroma Tumor microenvironment Cancer-associated fibroblasts Cancer stem cells Tumor-associated macrophages Hippo signaling pathway TEAD Tumor angiogenesis Exosomes
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Cardamom extract: An effective weapon in prevention of cardiorenal syndrome induced in rats by cisplatin and high-fat diet 认领 引用
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作者 Doha Mohamed Ibrahim Hamed Hoda B Mabrok 《World Journal of Nephrology》 2025年第3期144-158,共15页
BACKGROUND Overnutrition and unhealthy dietary habits are established risk factors for cardiovascular and renal diseases,which may lead to the development of cardiorenal syndrome(CRS).AIM To evaluate the cardiorenal p... BACKGROUND Overnutrition and unhealthy dietary habits are established risk factors for cardiovascular and renal diseases,which may lead to the development of cardiorenal syndrome(CRS).AIM To evaluate the cardiorenal protective potential of crude ethanol extract(CEE)of green cardamom(Elettaria cardamomum L.,Family Zingiberaceae).METHODS Rats were fed a high-fat diet to induce dyslipidemia and subsequently administered cisplatin(7.5 mg/kg)to induce CRS.CEE was administered orally to CRS rats at low(100 mg/kg)and high(200 mg/kg)doses for one month.Oxidative stress,inflammatory markers,cardiovascular disease markers,cardiac indices,and renal function(in plasma and urine)were assessed.The antioxidant activity and phenolic compound profile of CEE were evaluated.Additionally,the potential interactions of CEE phenolics with components of the Hippo signaling pathway(mammalian sterile 20-like kinase 1,large tumor suppressor kinase 1,Yes-associated protein,and transcriptional coactivator with PDZ-binding motif)were investigated using molecular docking.RESULTS Cisplatin administration combined with a high-fat diet effectively induced CRS,as evidenced by elevated oxidative stress,inflammation,and impaired cardiorenal parameters.Treatment with CEE at both doses improved these parameters,with the high dose demonstrating greater efficacy.CEE exhibited significant DPPH radical scavenging activity.Rosmarinic acid and gallic acid were identified as the major phenolic constituents.Molecular docking revealed strong binding affinities of rosmarinic acid and rutin with targets in the Hippo signaling pathway.CONCLUSION These findings demonstrate the cardioprotective and renoprotective potential of CEE as a phenolic-rich dietary supplement.CEE mitigated inflammation and oxidative stress,key contributors to CRS pathogenesis.Furthermore,molecular docking suggests that the phenolic compounds in CEE may exert protective effects by modulating the Hippo signaling pathway.Overall,CEE shows promise as a natural therapeutic agent for the prevention and/or management of cardiorenal syndrome. 展开更多
关键词 Cardiorenal syndrome Cardamom extract Hippo signaling pathway Oxidative stress Inflammatory markers Phenolic compounds
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The roles and regulation of Yes-associated protein 1 in stem cells 认领 引用 被引量：1
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作者 QING YIN CAIHONG LIU +3 位作者 WENYING JIANG HAIHUI GONG CHUNYUN LI ZUPING HE 《BIOCELL》 SCIE 2023年第1期33-39,共7页
Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of ... Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of YAP1 in mediating stem cell fate decisions are discussed,including cell proliferation,differentiation,and apoptosis.In general,YAP1 promotes the proliferation and differentiation of stem cells,including embryonic stem cells and adult stem cells.It inhibits apoptosis by binding to the transcription factors,e.g.,transcriptional enhanced associate domain(TEAD),Smad,runt-related transcription factor 1/2,p73,p63,and Erb84,to maintain tissue homeostasis.The translocalization of YAP1 in cellular nuclei and the phosphorylation in the cytoplasm work as important and unusual events for the activation of YAP1.Moreover,YAP1 serves as the crosstalk for the Hippo pathway and other signaling pathways,including the Wnt and Notch pathways.It is highlighted in this review that YAP1 is an essential regulator for stem cells that have significant applications in regenerative medicine and reproductive medicine. 展开更多
关键词 YAP1 Hippo signaling pathway Stem cells Fate determinations
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Mechanical stress-induced Hippo signaling in respect to primordial follicle development and polycystic ovary syndrome pathogenesis 认领 引用
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作者 Ling-Jin Xia Jing Du 《Reproductive and Developmental Medicine》 CAS CSCD 2022年第2期121-128,共8页
Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive disease that can cause infertility. The Hippo signaling pathway, a network highly conserved throughout evolution, maintains the balance between follicle... Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive disease that can cause infertility. The Hippo signaling pathway, a network highly conserved throughout evolution, maintains the balance between follicle proliferation and dormancy. Dynamic changes in primordial follicles cannot occur without the participation of biological signals and mechanical force;however, little is known about the mechanism by which biomechanical signaling triggers PCOS, especially in the context of primordial follicle development. To investigate the contribution of mechanical stress and the Hippo signaling pathway to the onset of PCOS, we searched the literature via the PubMed database, and inclusion and exclusion criteria were established to ensure the rigor of this research. We eventually included 54 publications in which Hippo signaling and mechanical force were suggested to play a vital role in the development of primordial follicles as well as elucidate the pathogenesis of PCOS. The Hippo pathway modulating follicle growth can be perturbed via extracellular mechanical stress caused by the stiff ovarian cortical environment in PCOS. Clinical intervention targeting the Hippo pathway can alter the activity of core Hippo members, such as the Yes-associated proteinranscriptional co-activator PDZ-binding motif complex. In some patients with PCOS, follicle overactivation can be attributed to the dysfunction of Hippo signal transduction. PCOS, a condition with various patterns, cannot be accurately explained by a single, specific mechanism. The present review identifies potential targets and therapeutic strategies for PCOS. 展开更多
关键词 Polycystic ovary syndrome Hippo signaling pathway Mechanical forces Extracellular matrix
LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein 认领 引用 被引量：3
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作者 Siyuan Yang Weizhi Xu +7 位作者 Cheng Liu Jiaqi Jin Xueying Li Yuhan Jiang Lei Zhang Xianbin Meng Jun Zhan Hongquan Zhang 《Science China(Life Sciences)》 SCIE CAS CSCD 2022年第1期129-141,共13页
Large tumor suppressor 1(LATS1)is the key kinase controlling activation of Hippo signalling pathway.Post-translational modifications of LATS1 modulate its kinase activity.However,detailed mechanism underlying LATS1 st... Large tumor suppressor 1(LATS1)is the key kinase controlling activation of Hippo signalling pathway.Post-translational modifications of LATS1 modulate its kinase activity.However,detailed mechanism underlying LATS1 stability and activation remains elusive.Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4.Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation.Mechanistically,LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation,leading to increased YAP nucleus translocation and promoted target gene expression.Functionally,LATS1-K751 Q,the acetylation mimic mutant potentiated lung cancer cell migration,invasion and tumor growth,whereas LATS1-K751 R,the acetylation deficient mutant inhibited these functions.Taken together,we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1. 展开更多
关键词 LATS1 acetylation LATS1 activation and inhibition Hippo signalling pathway lung adenocarcinoma
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Nuclear Dbf2-related Kinase 1 functions as tumor suppressor in glioblastoma by phosphorylation of Yes-associated protein 认领 引用
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作者 Bin Chen Bin Liu +3 位作者 Tao Yu Yun-Feng Han Chao Wu Zhen-Yu Wang 《Chinese Medical Journal》 SCIE CAS CSCD 2021年第17期2054-2065,共12页
Background:The Nuclear Dbf2-related(NDR1)kinase is a member of the NDR/LATS family,which was a supplementary of Hippo pathway.However,whether NDR1 could inhibit glioblastoma(GBM)growth by phosphorylating Yes-associate... Background:The Nuclear Dbf2-related(NDR1)kinase is a member of the NDR/LATS family,which was a supplementary of Hippo pathway.However,whether NDR1 could inhibit glioblastoma(GBM)growth by phosphorylating Yes-associated protein(YAP)remains unknown.Meanwhile,the role of NDR1 in GBM was not clear.This study aimed to investigate the role of NDR1-YAP pathway in GBM.Methods:Bioinformation analysis and immunohistochemistry(IHC)were performed to identify the expression of NDR1 in GBM.The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8,clone formation,immunofluorescence and flow cytometry,respectively.In addition,the xenograft tumor model was established as well.Protein interaction was examined by Coimmunoprecipitation and immunofluorescence to observe co-localization.Results:Bioinformation analysis and IHC of our patients’tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate.NDR1 could markedly reduce the proliferation and colony formation of U87 and U251.Furthermore,the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase.Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group.Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site.Meanwhile,NDR1 could mediate apoptosis process.Conclusion:In summary,our findings point out that NDR1 functions as a tumor suppressor in GBM.NDR1 is identified as a novel regulator of YAP,which gives us an in-depth comprehension of the Hippo signaling pathway. 展开更多
关键词 Glioblastoma Hippo signaling pathway Nuclear Dbf2-related Yes-associated protein
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