Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway

Chen, Xueran; Zhang, Shangrong; Wang, Zhen; Wang, Fengsong; Cao, Xinwang; Wu, Qiulian; Zhao, Chenggang; Ma, Huihui; Ye, Fang; Wang, Hongzhi; Fang, Zhiyou

doi:10.1186/s13046-018-0787-2

Cited by 54 publications

(53 citation statements)

References 55 publications

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“…Importantly, we also find that amoeboid melanoma cells express EMT-related genes driven by ROCK1/2. Rho-ROCK1/2 signalling has been shown in other models to regulate actin cytoskeleton rearrangements during EMT 47 while promoting transcriptional changes through activating p38 signalling 48 , 49 . Interestingly, ROCK1/2 regulates TGFβ expression in our EMT array and TGFβ signalling is one of the top networks associated with the EMT gene signature regulated by ROCK1/2.…”

Section: Discussionmentioning

confidence: 99%

WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

et al. 2020

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Melanoma is a highly aggressive tumour that can metastasize very early in disease progression. Notably, melanoma can disseminate using amoeboid invasive strategies. We show here that high Myosin II activity, high levels of ki-67 and high tumour-initiating abilities are characteristic of invasive amoeboid melanoma cells. Mechanistically, we find that WNT11-FZD7-DAAM1 activates Rho-ROCK1/2-Myosin II and plays a crucial role in regulating tumour-initiating potential, local invasion and distant metastasis formation. Importantly, amoeboid melanoma cells express both proliferative and invasive gene signatures. As such, invasive fronts of human and mouse melanomas are enriched in amoeboid cells that are also ki-67 positive. This pattern is further enhanced in metastatic lesions. We propose eradication of amoeboid melanoma cells after surgical removal as a therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

et al. 2020

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“…Because of the essential roles of LCSCs in initiation and recurrence, identification of key candidate miRNAs that regulate LCSCs and exploration of their therapeutic potential in HCC may be helpful for improving treatment [ 16 ]. To better identify the miRNAs involved in the LCSCs self-renewal and differentiation process, we analyzed the genome-wide transcriptional profiling with miRNA microarray in different stages of LCSC cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-302a/d inhibits the self-renewal capability and cell cycle entry of liver cancer stem cells by targeting the E2F7/AKT axis

et al. 2018

J Exp Clin Cancer Res

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BackgroundThere is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs.MethodsMiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro. The expression and correlation of miRNA-302a/d and E2F7 in HCC patients was evaluated by quantitative PCR and Kaplan–Meier survival analysis.ResultsWe found that the miRNA-302 family was downregulated during the spheroid formation of HCC cells and patients with lower miRNA-302a/d expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. Furthermore, concomitant low expression of miRNA-302a/d and high expression of E2F7 correlated with a shorter median OS and PFS in HCC patients. Cellular functional analysis demonstrated that miRNA-302a/d negatively regulates self-renewal capability and cell cycle entry of liver cancer stem cells via suppression of its target gene E2F7 and its downstream AKT/β-catenin/CCND1 signaling pathway.ConclusionsOur data provide the first evidence that E2F7 is a direct target of miRNA-302a/d and miRNA-302a/d inhibits the stemness of LCSCs and proliferation of HCC cells by targeting the E2F7/AKT/β-catenin/CCND1 signaling pathway.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0927-8) contains supplementary material, which is available to authorized users.

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“…RHOA encodes a member of the Rho family of small GTPases that acts as a molecular switch in the signal transduction cascade [33]. Overexpression of this gene is associated with tumor cell proliferation and metastasis [34,35].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of aberrantly expressed methylation genes in human hepatocellular carcinoma

Zhen

Ning

et al. 2020

Bioscience Reports

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Objectives: To identify the prognostic value of aberrantly methylated differentially expressed genes (DEGs) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms of tumorigenesis. Methods: Gene expression profiles (GSE65372 and GSE37988) were analyzed using GEO2R to obtain aberrantly methylated DEGs. Functional enrichment analysis of screened genes was performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Cytoscape software was used to analyze the PPI network and to select hub genes. Transcriptional and proteinic expression data of hub genes were obtained through UALCAN and the Human Protein Reference Database. Finally, we analyzed the prognostic value of hub genes with the Kaplan-Meier Plotter and MethSurv database. Results: In total, 24 up-hypomethylated oncogenes and 37 down-hypermethylated tumor suppressor genes (TSGs) were identified, and 8 hub genes, including 4 up-hypomethylated oncogenes (CDC5L, MERTK, RHOA and YBX1) and 4 down-hypermethylated TSGs (BCR, DFFA, SCUBE2, TP63), were selected by PPI. Higher expression of methylated CDC5L-cg05671347, MERTK-cg08279316, RHOA-cg05657651 and YBX1-cg16306148, and lower expression of methylated BCR-cg25410636, DFFA-cg20696875, SCUBE2-cg19000089 and TP63-cg06520450, were associated with better overall survival (OS) in HCC patients. Multivariate analysis also showed they were independent prognostic factors for OS of HCC patients. Conclusions: In summary, different expression of methylated genes above mentioned were associated with better prognosis in HCC patients. Altering the methylation status of these genes may be a therapeutic target for HCC, but it should be further evaluated in clinical studies.

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Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway

Cited by 54 publications

References 55 publications

WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

MicroRNA-302a/d inhibits the self-renewal capability and cell cycle entry of liver cancer stem cells by targeting the E2F7/AKT axis

Prognostic value of aberrantly expressed methylation genes in human hepatocellular carcinoma

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