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ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via Driving DHFR Transcriptional Activation 认领 引用
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作者 Yongle Qiu Kunshan Li +5 位作者 Wenjing Wang Wenjuan Zhang Jilun Liu Yang Bai Fei Xu Jie Guo 《Oncology Research》 SCIE 2026年第1期458-478,共21页
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism... Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC. 展开更多
关键词 Oral squamous cell carcinoma vasculogenic mimicry metastasis dihydrofolate reductase ETS transcription factor ELK4
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Unraveling vascular mechanisms in melanoma:roles of angiogenesis and vasculogenic mimicry in tumor progression and therapeutic resistance 认领 引用
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作者 Simona Serratì Lucia Raho +7 位作者 Gisella De Giosa Letizia Porcelli Roberta Di Fonte Rossella Fasano Pedro Miguel Lacal Grazia Graziani Rosa Maria Iacobazzi Amalia Azzariti 《Cancer Biology & Medicine》 SCIE CAS CSCD 2025年第11期1327-1352,共26页
Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogeni... Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance.Angiogenesis,driven primarily by VEGF/VEGFR signaling,is critical for tumor sustenance but is often insufficient under hypoxic conditions,prompting melanoma cells to adapt by forming vascular-like structures(i.e.,vasculogenic mimicry).These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis.Molecular drivers,including VE-cadherin,EphA2,and hypoxia-inducible factors,have been identified as key regulators of these processes.Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry.The review highlights the need for therapeutic strategies targeting both mechanisms,emphasizing the importance of combination treatments to overcome resistance.Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes. 展开更多
关键词 Melanoma angiogenesis vasculogenic mimicry
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Data Mining-Driven: Identification of Potential Traditional Chinese Medicine Categories Targeting Vasculogenic Mimicry in Esophageal Cancer 认领 引用
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作者 Yunqin Wang Yu Wang +3 位作者 Qian Zhang Ruoshui Xia Yanqing Liu Jue Chen 《Proceedings of Anticancer Research》 2025年第5期81-91,共11页
Background:Vasculogenic mimicry refers to a specialized tumor microvasculature independently formed by tumor cells,which facilitates the recurrence,metastasis,and therapeutic resistance in esophageal cancer.Within the... Background:Vasculogenic mimicry refers to a specialized tumor microvasculature independently formed by tumor cells,which facilitates the recurrence,metastasis,and therapeutic resistance in esophageal cancer.Within the framework of traditional Chinese medicine(TCM)theory,there is currently no clear conceptual classification or diagnostic-therapeutic principles for this phenomenon.Objective:To explore traditional Chinese medicine(TCM)herbs and syndrome factors related to the treatment of vasculogenic mimicry in esophageal cancer,and to provide a reference for clarifying the TCM clinical syndromes of vasculogenic mimicry in esophageal cancer.Methods:Based on public databases such as TCMSP,CNKI,and PubMed,TCM herbs related to esophageal cancer,clinical medications,and herbs inhibiting vasculogenic mimicry were retrieved.The herbs collected from multiple databases were standardized,collated,and cross-analyzed,and core herbs were screened for further analysis.Results:Among the public databases,herbs inhibiting vasculogenic mimicry and commonly used clinical herbs for esophageal cancer were mainly of the blood-activating and stasis-resolving type(Huoxue Huayu).In contrast,esophageal cancer-related herbs in the TCMSP database were mainly of the heat-clearing and toxin-resolving type(Qingre Jiedu).A total of 22 TCM herbs related to vasculogenic mimicry in esophageal cancer were identified,mainly blood-activating and stasis-resolving herbs,involving three syndrome factors:“blood stasis(Xueyu),Qi deficiency(Qixu),and Qi stagnation(Qizhi).”Conclusion:Vasculogenic mimicry can promote the progression of esophageal cancer,and blood-activating and stasis-resolving herbs may improve the prognosis of patients with esophageal cancer. 展开更多
关键词 Esophageal cancer Vasculogenic mimicry Recurrence and metastasis Traditional Chinese medicine
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Competition and the evolution of imperfect mimicry 认领 引用 被引量：1
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作者 David W.PFENNIG David W.KIKUCHI 《Current Zoology》 SCIE CAS CSCD 2012年第4期608-619,共12页
Mimicry is widely used to exemplify natural selection's power in promoting adaptation.Nonetheless,it has become increasingly clear that mimicry is frequently imprecise.Indeed,the phenotypic match is often poor bet... Mimicry is widely used to exemplify natural selection's power in promoting adaptation.Nonetheless,it has become increasingly clear that mimicry is frequently imprecise.Indeed,the phenotypic match is often poor between mimics and models in many Batesian mimicry complexes and among co-mimics in many Mtillerian mimicry complexes.Here,we consider whether such imperfect mimicry represents an evolutionary compromise between predator-mediated selection favoring mimetic conver-gence on the one hand and competitively mediated selection favoring divergence on the other hand.Specifically,for mimicry to be effective,mimics and their models/co-mimics should occur together.Yet,co-occurring species that are phenotypically similar often compete for resources,successful reproduction,or both.As an adaptive response to minimize such costly interactions,in-teracting species may diverge phenotypically through an evolutionary process known as character displacement.Such divergence between mimics and their models/co-mimics may thereby result in imperfect mimicry.We review the various ways in which character displacement could promote imprecise mimicry,describe the conditions under which this process may be especially likely to produce imperfect mimicry,examine a possible case study,and discuss avenues for future research.Generally,character displacement may play an underappreciated role in fostering inexact mimicry. 展开更多
关键词 Batesian mimicry Character displacement Hybridization MtUlerian mimicry Reproductive interference Selectivetrade-off
HIF-1α induces VE-cadherin expression and modulates vasculogenic mimicry in esophageal carcinoma cells 认领 引用 被引量：32
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作者 Na-Na Tang Hong Zhu +7 位作者 Hong-Jie Zhang Wei-Feng Zhang Hai-Lin Jin Lu Wang Pin Wang Gui-Jun He Bo Hao Rui-Hua Shi 《World Journal of Gastroenterology》 SCIE CAS 2014年第47期17894-17904,共11页
AIM: To investigate whether hypoxia inducible factor (HIF)-1&#x003b1; modulates vasculogenic mimicry (VM) by upregulating VE-cadherin expression in esophageal squamous cell carcinoma (ESCC).
关键词 Esophageal squamous cell carcinoma Hypoxia-inducible factor-1α VE-cadherin RNA interference Vasculogenic mimicry
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Cancer stem-like cells directly participate in vasculogenic mimicry channels in triple-negative breast cancer 认领 引用 被引量：9
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作者 Huizhi Sun Nan Yao +6 位作者 Siqi Cheng Linqi Li Shiqi Liu Zhao Yang Guanjie Shang Danfang Zhang Zhi Yao 《Cancer Biology & Medicine》 SCIE CAS CSCD 2019年第2期299-311,共13页
Objective: Vasculogenic mimicry(VM) channels that are lined by tumor cells are a functional blood supply in malignant tumors.However, the role of VM-initiating cells remains poorly understood. Cancer stem-like cells(C... Objective: Vasculogenic mimicry(VM) channels that are lined by tumor cells are a functional blood supply in malignant tumors.However, the role of VM-initiating cells remains poorly understood. Cancer stem-like cells(CSCs) are positively correlated with VM. In this study, triple-negative breast cancer(TNBC) enriched with CSCs was used to investigate the relationship between VM and CSCs.Methods: The expression of several CSC markers was detected by immunohistochemistry in 100 human breast cancer samples.The clinical significance of CSC markers and the relationship between VM, CSCs, breast cancer subtypes, and VM-associated proteins were analyzed. CD133+ and ALDH+ human and mouse TNBC cells were isolated by FACS to examine the ability of VM formation and the spatial relationship between VM and CSCs.Results: CSCs were associated with TNBC subtype and VM in human invasive breast cancer. CSCs in TNBC MDA-MB-231 cells formed more VM channels and expressed more molecules promoting VM than the non-TNBC MCF-7 cells in vitro. MDA-MB-231 cells that encircled VM channels on Matrigel expressed CD133. Moreover, CSCs were located near VM channels in the 3D reconstructed blood supply system in human TNBC grafts. The CD133+ and ALDH+ cells isolated from TA2 mouse breast cancer formed more VM channels in vivo.Conclusions: CSCs line VM channels directly. Additionally, CSCs provide more VM-related molecules to synergize VM formation. The signaling pathways that control CSC differentiation may also be potential treatment targets for TNBC. 展开更多
关键词 Vasculogenic mimicry triple-negative breast cancer cancer stem-like cells ALDH1 CD 133
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Intersexual mimicry and imperfect deceit of a threatened aquatic herb Ottelia acuminata 认领 引用 被引量：6
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作者 Jing Yang Yang Niu +2 位作者 Wei-Bang Sun Xiang-Hai Cai Gao Chen 《Journal of Systematics and Evolution》 SCIE CAS CSCD 2022年第2期377-385,共9页
Mimicry of non-rewarding flowers to rewarding flowers has been accepted as a strategy to improve pollination success in angiosperms.It has been proposed that this mechanism depends on whether potential pollinators can... Mimicry of non-rewarding flowers to rewarding flowers has been accepted as a strategy to improve pollination success in angiosperms.It has been proposed that this mechanism depends on whether potential pollinators can discriminate between the flowers.In this study,the intersexual mimicry and deceit pollination were studied in a threatened dioecious aquatic herb,Ottelia acuminata.Its female flowers resemble male flowers in morphology and odor compounds,to avoid discrimination by pollinators and outcompete male flowers in attracting the pollinators using stronger scents and bigger flowers.However,an obvious visit bias of its pollinator(Apis cerana)to male flowers was detected,suggesting that bees can distinguish the rewarding males from non-rewarding females.Although the deceit was not successful,pollination was not seriously undermined because pollen limitation was found to be low in the sampled natural population.We speculate that,due to“accidental”visits on female flowers and“mistake”pollinations,pollen limitation could be mitigated by a high frequency of pollen donors,and is correlated with the size and sex ratio of a population.Ottelia acuminata is a threatened dioecious aquatic herb.We suggest that developing multi-stakeholder coalitions should be encouraged to save the threatened edible and ornamental plant species in China.We hope this study could provide new insights into understanding of the role of intersexual mimicry in other flowering plants. 展开更多
关键词 deceit pollination dioecy intersexual mimicry Ottelia acuminata pollinator preference sex ratio
Expression of Maspin in Non-small Cell Lung Cancer and Its Relationship to Vasculogenic Mimicry 认领 引用 被引量：23
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作者 武世伍 俞岚 +3 位作者 承泽农 宋文庆 周蕾 陶仪声 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2012年第3期346-352,共7页
Maspin belongs to the serine protease inhibitor （serpin） family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the express... Maspin belongs to the serine protease inhibitor （serpin） family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer （NSCLC） and its relationship to vasculogenic mimicry （VM）. A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density （MVD） and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% （77/160） and 36.9% （59/160）, respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively （P〈0.05）. VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time （all P〈0.05）. The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma （P〈0.05）. The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC （P〈0.05）. It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC. 展开更多
关键词 non-small cell lung cancer maspin vasculogenic mimicry microvessel density prognosis
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Molecular mimicry in Helicobacter pylori infections 认领 引用 被引量：39
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作者 magdalena chmiela weronika gonciarz 《World Journal of Gastroenterology》 SCIE CAS 2017年第22期3964-3977,共14页
Gram-negative bacteria Helicobacter pylori(H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tis... Gram-negative bacteria Helicobacter pylori(H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases,diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host. 展开更多
关键词 Helicobacter pylori Molecular mimicry Anti-self response Extragastric effects
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Study on vasculogenic mimicry in malignant esophageal stromal tumors 认领 引用 被引量：26
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作者 Hui Zhao Xiao-Meng Gu 《World Journal of Gastroenterology》 SCIE CAS 2008年第15期2430-2433,共4页
AIM: To investigate whether malignant esophageal stromal tumors contain PAS-positive patterned matrix-associated vascular channels, which are lined by tumor cells, but not vascular endothelial cells. That is vasculoge... AIM: To investigate whether malignant esophageal stromal tumors contain PAS-positive patterned matrix-associated vascular channels, which are lined by tumor cells, but not vascular endothelial cells. That is vasculogenic mimicry (VM) independent of tumor angiogenesis. METHODS: Thirty-six tissue samples of malignant esophageal stromal tumors were analyzed. Tissue sections were stained for Vascular endothelial growth factor (VEGF), CD31 and periodic acid Schiff (PAS). The level of VEGF, the microvascular density (MVD) and the vasculogenic mimicry density (VMD) were determined. RESULTS: PAS-positive patterned matrix-associated vascular channels were detected in 33.3% (12/36) of tumor samples. Within these patterned channels, red blood cells were found. The level of VEGF and the MVD in tumors containing patterned channels were significantly higher than those in tumors not containing patterned channels (P < 0.05). At the same time, the malignant degree of tumors was higher, the proportions of tumors containing patterned channels were not only more, but also in the each kind of tumors containing patterned channels. CONCLUSION: In malignant esophageal stromal tumors, a VM mechanism causes some tumor cells to deform themselves and secrete extracellular matrix; thus, PAS-positive patterned matrix-associated vascular channels appear and supplying blood to the tumors to sustain their growth and metastasis. 展开更多
关键词 Esophageal Stromal tumors Malignanttumor Tumor angiogenesis Vasculogenic mimicry
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Vasculogenic Mimicry and Aberrant Expression of HIF-lα/E-cad Are Associated with Worse Prognosis of Esophageal Squamous Cell Carcinoma 认领 引用 被引量：11
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作者 柴大敏 鲍正齐 +3 位作者 胡建国 马莉 冯振中 陶仪声 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2013年第3期385-391,共7页
Summary： This study aims to find good markers for predicting the prognosis of patients with eso- phageal squamous cell carcinoma （ESCC）. Vasculogenic mimicry （VM） and the expression of hy- poxia inducible factor-... Summary： This study aims to find good markers for predicting the prognosis of patients with eso- phageal squamous cell carcinoma （ESCC）. Vasculogenic mimicry （VM） and the expression of hy- poxia inducible factor-1α（HIF-1α）/E-cad protein in ESCC were investigated by immunostaining. The association between VM, HIF-1α/E-cad and clinicopathologic characteristics and 5-year-survival rate of patients with ESCC was analyzed. A total of 160 ESCC specimens were involved in this study and 28 specimens of normal esophageal mucosa served as controls. VM channels were identified in 78 （48.75%） of the 160 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of high-expression of HIF-1αand E-cad in ESCC were 43.75% and 38.75%, while the rates in control were 17.86% and 71.43%, respectively （P〈0.05 for all）. VM and the expression levels of HIF-1α and E-cad were significantly related to lymph node metastasis, serosa infiltration, PTNM staging and 5-year-survival rates of patients with ESCC （P〈0.05 for all）. VM was positively corre- lated with HIF-1α but negatively with E-cad, and HIF-let was negatively correlated with E-cad （P〈0.001 for all）. The 5-year-survival rate of patients with ESCC was 6.41% （5/78） in VM group and 65% （52/82） in non-VM group, 7.14% （5/70） in high HIF-1α expression group and 57.78% （52/90） in low HIF-1α expression group. Oppositely, the 5-year-survival rate in high E-cad expression group was 80.65% （50/62） and that in low E-cad expression group was 7.37% （7/98） （P〈0.05 for all）. Cox multifactor regression analysis indicated that lymph node metastasis, PTNM stage, VM and expres- sion levels of HIF-1α and E-cad were independent risk factors of patients with ESCC （P〈0.05 for all）. Combined detection ofVM, HIF-1α and E-cad plays an important role in predicting the invasion, me- tastasis and prognosis of patients with ESCC. 展开更多
关键词 esophageal squamous cell carcinoma vasculogenic mimicry hypoxia inducible factor-let E-cadherin prognosis
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Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy 认领 引用 被引量：21
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作者 Yue-Zu Fan Wei Sun 《World Journal of Gastrointestinal Surgery》 2010年第4期117-127,共11页
"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in t... "Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy. 展开更多
关键词 Tumor-target therapy Signaling pathways High aggressive tumor Molecular regulation Prognosis Vasculogenic mimicry
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Pilot Study of Molecular Mechanism on Vasculogenic Mimicry in Bi-directional Differentiated Malignant Tumors 认领 引用 被引量：7
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作者 孙保存 张诗武 +2 位作者 赵秀兰 张丹芳 郝希山 《The Chinese-German Journal of Clinical Oncology》 2005年第1期50-52,68,共3页
Objective: To investigate the role of collagen IV and PAS positive substancesecreted by tumor cells in vasculogenic mimicry (VM) and the effects of VM on tumor cells expressingVEGF. Methods: 158 cases of bi-direction ... Objective: To investigate the role of collagen IV and PAS positive substancesecreted by tumor cells in vasculogenic mimicry (VM) and the effects of VM on tumor cells expressingVEGF. Methods: 158 cases of bi-direction differential malignant tumor specimens withparaffin-embedded were enrolled into our study and made tissue microarray which were dual-stainedwith CD31-PAS and stained with collagen IV. The difference of the areas and distribution withpattern surrounded by between CD31 and PAS positive respectively were identified via grid-counting,as well as the difference of VEGF expression with VE absent and present. Results: The basementmembrane of VM was both PAS and collagen IV positive. VEGF expression in the bi-directiondifferential malignant tumor was higher VM-absent than VM-present and the difference wasstatistically significance in malignant melanoma and alveolar rhabdomyosarcoma (P 【 0.05).Conclusion: PAS positive substance and collagen IV compose the wall of VE and VE could provide theoxygen and nutrition for tumor growth and progression. 展开更多
关键词 bi-direction differential malignant tumor vasculogenic mimicry dual-staining tissue microarray
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Notch4 Inhibition Suppresses Invasion and Vasculogenic Mimicry Formation of Hepatocellular Carcinoma Cells 认领 引用 被引量：8
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作者 程锐 蔡欣然 +1 位作者 柯坤 陈燕凌 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2017年第5期719-725,共7页
Vasculogenic mimicry（VM） is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma（HCC）. It has provided new insights into tum... Vasculogenic mimicry（VM） is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma（HCC）. It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy. The molecular events underlying the process of VM formation are still poorly understood. In this study, we attempted to elucidate the relationship between Notch4 and VM formation in HCC. An effective si RNA lentiviral vector targeting Notch4 was constructed and transfected into Bel7402, a HCC cell line. VM networks were observed with a microscope in a 3 dimensional cell culture system. Cell migration and invasion were evaluated using wound healing and transwell assays. Matrix metalloproteinases（MMPs） activity was detected by gelatin zymography. Furthermore, the role of Notch4 inhibition in Bel7402 cells in vivo was examined in subcutaneous xenograft tumor model of mice. The results showed that downregulation of Notch4 destroyed VM network formation and inhibited migration and invasion of tumor cells in vitro（P〈0.05）. In vivo, tumor growth was also inhibited in subcutaneous xenograft model（P〈0.05）. The potential mechanisms might be related with down-regulation of MT1-MMP, MMP-2, MMP-9 expression and inhibition of the activation of MMP2 and MMP9. These results indicated that Notch4 may play an important role in VM formation and tumor invasion in HCC. Related molecular pathways may be used as novel therapeutic targets for HCC antiangiogenesis therapy. 展开更多
关键词 vasculogenic mimicry hepatocellular carcinoma invasion Notch4 matrix metalloproteinase
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The function of animal ‘eyespots’:Conspicuousness but not eye mimicry is key 认领 引用 被引量：2
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作者 Martin STEVENS Abi CANTOR +1 位作者 Julia GRAHAM Isabel S.WINNEY 《Current Zoology》 CAS 北大核心 2009年第5期319-326,共8页
Many animals are marked with conspicuous circular features often called ＇eyespots＇, which intimidate predators, preventing or halting an attack. It has long been assumed that eyespots work by mimicking the eyes of l... Many animals are marked with conspicuous circular features often called ＇eyespots＇, which intimidate predators, preventing or halting an attack. It has long been assumed that eyespots work by mimicking the eyes of larger animals, but recent experiments have indicated that conspicuousness and contrast is important in eyespot function, and not eye mimicry. We undertake two further experiments to distinguish between the conspicuousness and mimicry hypotheses, by using artificial prey presented to wild avian predators in the field. In experiment 1, we test if eyespot effectiveness depends on the marking shape （bar or circle） and arrangement （eye-like and non-eye-like positions）. We find no difference between shapes or arrangement; all spots were equally effective in scaring birds. In experiment 2, we test if the often yellow and black colors of eyespots mimic the eyes of birds of prey. We find no effect of shape, and no advantage to yellow and black spots over non-eye-like but equally conspicuous colors. The consistent finding is that eyespot function lies in being a conspicuous signal to predators, and not necessarily due to eye mimicry [ Current Zoology 55 （5） ： 319 - 326, 2009]. 展开更多
关键词 Eyespots Conspicuousness Mimicry Predation Protective coloration
Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways 认领 引用 被引量：2
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作者 Pengxiang Min Yingying Li +7 位作者 Cuirong Wang Junting Fan Shangming Liu Xiang Chen Yamin Tang Feng Han Aixia Zhang Lili Feng 《Journal of Biomedical Research》 CAS CSCD 2024年第4期322-333,共12页
Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to t... Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM. 展开更多
关键词 moroidin vasculogenic mimicry glioblastoma EMT β-catenin
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Molecular mimicry and multiple sclerosis 认领 引用 被引量：1
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作者 Michael Namaka Sabina Kapoor +7 位作者 Leann Simms Christine Leong Amy Grossberndt Michael Prouta Emma Frost Farid Esfahani Andrew Gomori Michael R. Mulvey 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第17期1322-1333,共12页
Multiple sclerosis （MS） is a chronic demyelinating disease of the central nervous system. Although the exact underlying mechanism leading to myelin destruction is unknown, the molecular mimicry theory is the most co... Multiple sclerosis （MS） is a chronic demyelinating disease of the central nervous system. Although the exact underlying mechanism leading to myelin destruction is unknown, the molecular mimicry theory is the most commonly acknowledged elucidation of MS pathology. Although various antigens have been associated with MS induction, this review presents studies focused on key bacterial and viral antigens that lead to the development of MS. The research specific to a molecular mimicry theory of MS via each implicated agent is weak; however, collectively the reports provide credible support for this theory. Given that homologous sequences are not required to lead to antigenic cross-reactivity, it is reasonable to conclude that certain viral and bacterial antigens with 5-10 similar amino acids in sequence can lead to self destruction of similar myelin sequences. Thus, this literature review has provided insight to further the understanding of the etiology of multiple sclerosis. 展开更多
关键词 antibodies autoimmune diseases molecular mimicry multiple sclerosis neurodegenerative diseases
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ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells 认领 引用 被引量：1
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作者 Jing Xie Jiaxin Tang +3 位作者 Yuan Li Xue Kong Wei Wang Haibo Wu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第8期834-849,共16页
Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serinehreonine kinase... Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serinehreonine kinase activation,which confers chemoradiotherapy resistance,remains unclear.Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied.Results VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(rs=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2.Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM. 展开更多
关键词 Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell
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Downregulation of Astrocyte Elevated Gene-1 Expression Combined with All-Trans Retinoic Acid Inhibits Development of Vasculogenic Mimicry and Angiogenesis in Glioma 认领 引用 被引量：1
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作者 Chen LIANG Ling YANG +1 位作者 Shi-wen GUO Rui-chun LI 《Current Medical Science》 SCIE CAS 2022年第2期397-406,共10页
Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in gl... Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in glioma.Methods U87 glioma cells were transfected with AEG-1 shRNA lentiviral vectors(U87-siAEG-1)and incubated in a medium containing 20µmol/L ATRA.Matrigel-based tube formation assay was performed to evaluate VM formation,and the cell counting kit-8(CCK-8)assay was used to analyze the proliferation of glioma cells in vitro.Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to investigate the mRNA and protein expression of related genes,respectively.Glioma xenograft models were generated via subcutaneous implantation of glioma cells in nude mice.Tumor-bearing mice received an intraperitoneal injection of ATRA(10 mg/kg per day).Immunohistochemistry was used to evaluate the expression of related genes and the microvessel density(MVD)in glioma xenograft models.CD34/periodic acid-Schiff double staining was performed to detect VM channels in vivo.The volume and weight of tumors were measured,and a tumor growth curve was drawn to evaluate tumor growth.Results A combination of ATRA intervention and downregulation of AEG-1 expression significantly inhibited the proliferation of glioma cells in vitro and glioma VM formation in vitro and in vivo.It also significantly decreased MVD and inhibited tumor growth.Further,the expression levels of matrix metalloproteinase(MMP)-2,MMP-9,vascular endothelial-cadherin(VE-cadherin),and vascular endothelial growth factor(VEGF)in glioma significantly decreased in vivo and in vivo.Conclusion Hence,a combinatorial approach might be effective in treating glioma through regulating MMP-2,MMP-9,VEGF,and VE-cadherin expression. 展开更多
关键词 astrocyte elevated gene-1 glioma all-trans retinoic acid vasculogenic mimicry angiogenesis
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Behavioral snake mimicry in breeding tits 认领 引用 被引量：1
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作者 Anders Pape MФLLER Einar FLENSTED-JENSEN Wei LIANG 《Current Zoology》 SCIE CAS CSCD 2021年第1期27-33,共7页
Many animals mimic the behavior or the appearance of venomous snakes.When humans or other potential predators place their hand near the nest of tits belonging to the family Paridae(and a few other species),the incubat... Many animals mimic the behavior or the appearance of venomous snakes.When humans or other potential predators place their hand near the nest of tits belonging to the family Paridae(and a few other species),the incubating female performs a hissing display that mimics the inhalation hiss of a viper or another snake.They hiss vigorously while lunging their head forward and shaking their wings and tail,repeating this behavior several times.The structure of the hiss in tits is similar to that of the inhalation hiss of a snake,providing evidence of significant convergence of the mimic toward the model.The behavior of individual females is repeatable among tri als.Individuals that flew away from their nest box only performed the hissing display on 6%of later trials,when present at their box,whereas individuals that did not fly away hissed on 28% of occasions,consistent with great tits Parus major either cautiously flying away or staying put on their nest while actively defending it.Individuals that flew away produced fewer chicks than individuals that stayed and hissed.The hissing display was more common when snakes were more abundant:1)When breeding late during the season;2)when breeding at sites with more snakes;and 3)when breeding in subtropical and tropical China with a higher abundance of snakes than in Denmark with a lower abundance.The frequency of nest predation was higher in sites with no snakes,and the frequency of predation increased with decreasing frequency of hissing display.These findings are consistent with expectations for frequency-dependent selection acting on snake mimicry. 展开更多
关键词 Batesian mimicry frequency-dependent selection hissing display personaliy tits
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