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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 | |
Chen,Xueran1,2; Zhang,Shangrong1,2; Wang,Zhen1,3; Wang,Fengsong4; Cao,Xinwang4; Wu,Quan5; Zhao,Chenggang1,3; Ma,Huihui3,6; Ye,Fang2; Wang,Hongzhi1,2; Fang,Zhiyou1,2 | |
2018-06-28 | |
发表期刊 | Journal of Experimental & Clinical Cancer Research |
ISSN | 1756-9966 |
通讯作者 | Fang,Zhiyou(z.fang@cmpt.ac.cn) |
摘要 | AbstractBackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with HCC. Hypoxia triggers the epithelial-mesenchymal transition (EMT) of cancer cells, which enhances their malignant character and elevates metastatic risk. Supervillin associates tightly with the membrane and cytoskeleton, promoting cell motility, invasiveness, and cell survival. However, the roles of supervillin in HCC metastasis remain unclear.MethodsTissue microarray technology was used to immunohistochemically stain for supervillin antibody in 173 HCC tissue specimens and expression levels correlated with the clinicopathological variables. Tumor cell motility and invasiveness, as well as changes in the mRNA expression levels of genes associated with cancer cell EMT, were investigated. The relationship between supervillin and Rho GTPases was examined using Co-IP and GST pull-down.ResultsHypoxia-induced upregulation of supervillin promoted cancer cell migration and invasion via the activation of the ERK/p38 pathway downstream of RhoA/ROCK signaling. Furthermore, supervillin regulated the expression of EMT genes during hypoxia and accelerated the metastasis of HCC in vivo.ConclusionsHypoxia-induced increase in supervillin expression is a significant and independent predictor of cancer metastasis, which leads to poor survival in HCC patients. Our results suggest that supervillin may be a candidate prognostic factor for HCC and a valuable target for therapy. |
关键词 | Supervillin RhoA/ROCK ERK/P38 EMT HCC |
DOI | 10.1186/s13046-018-0787-2 |
语种 | 英语 |
WOS记录号 | BMC:10.1186/s13046-018-0787-2 |
出版者 | BioMed Central |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.hfcas.ac.cn:8080/handle/334002/42794 |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Fang,Zhiyou |
作者单位 | 1. 2. 3. 4. 5. 6. |
推荐引用方式 GB/T 7714 | Chen,Xueran,Zhang,Shangrong,Wang,Zhen,et al. Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway[J]. Journal of Experimental & Clinical Cancer Research,2018,37. |
APA | Chen,Xueran.,Zhang,Shangrong.,Wang,Zhen.,Wang,Fengsong.,Cao,Xinwang.,...&Fang,Zhiyou.(2018).Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway.Journal of Experimental & Clinical Cancer Research,37. |
MLA | Chen,Xueran,et al."Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway".Journal of Experimental & Clinical Cancer Research 37(2018). |
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