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

doi:10.1186/s13046-018-0787-2

HFCAS OpenIR

	Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway
	Chen,Xueran 1,2; Zhang,Shangrong 1,2; Wang,Zhen 1,3; Wang,Fengsong 4; Cao,Xinwang 4; Wu,Quan 5; Zhao,Chenggang 1,3; Ma,Huihui 3,6; Ye,Fang2 ; Wang,Hongzhi1,2 ; Fang,Zhiyou 1,2
	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).