Back to Search
Start Over
ARHGEF10L contributes to liver tumorigenesis through RhoA-ROCK1 signaling and the epithelial-mesenchymal transition
- Source :
- Experimental cell research. 374(1)
- Publication Year :
- 2018
-
Abstract
- Aberrant activity of Rho small G-proteins and their regulators plays an important role in tumorigenesis. Rho guanine nucleotide exchange factor 10-Like (ARHGEF10L) is a member of the RhoGEF family that promotes the active GTP-bound state of Rho GTPases. This study used the Illumina GoldenGate microassay, Sequenom MassARRAY and TaqMan to analyze possible correlations between tag single nucleotide polymorphisms (tag SNPs) in the ARHGEF10L locus and various tumor risks. The genotyping analyses demonstrated a strong association of rs2244444 and rs12732894 with liver cancer. Western blotting and immunohistochemistry also revealed increased expression of ARHGEF10L in hepatocellular carcinoma tissues. Furthermore, increased cell proliferation, cell migration and RhoA activity; increased expression of Rho-associated coiled-coil kinase-1 (ROCK1), phospho- Ezrin/Radixin/Moesin (ERM), vimentin, N-cadherin and Slug, and decreased E-cadherin expression were detected in hepatocellular carcinoma cell Bel-7402 and HepG2 cells with transfection of ARHGEF10L-expressing plasmids. Opposite results were obtained in the two cell lines with transfection of anti-ARHGEF10L siRNA. Tumor-bearing mice were generated with Bel-7402 cells transfected with lentivirus vectors packaging short hairpin ARHGEF10L RNA. The xenograft tumors with the inhibited ARHGEF10L expression showed decreased tumor growth and expression of vimentin, N-cadherin and Slug. Additionally, decreased phospho-ERM expression was detected in Bel-7402 and HepG2 cells with transfection of anti-ROCK1 siRNA and increased expression of ROCK1 was detected in hepatocellular carcinoma tissues. E-cadherin, vimentin, N-cadherin and Slug are markers of the epithelial-to-mesenchymal transition (EMT). ROCK1, phospho-ERM and EMT have been reported to promote tumor cell proliferation, metastasis and angiogenesis. Our study suggests that increased expression of ARHGEF10L stimulates hepatocellular tumorigenesis by activating the RhoA-ROCK1- phospho ERM pathway and EMT.
- Subjects :
- 0301 basic medicine
Male
RHOA
Epithelial-Mesenchymal Transition
Carcinogenesis
Moesin
Mice, Nude
Vimentin
Biology
03 medical and health sciences
0302 clinical medicine
Ezrin
Cell Movement
Risk Factors
Cell Line, Tumor
Animals
Humans
ROCK1
Genetic Predisposition to Disease
Epithelial–mesenchymal transition
Aged
Cell Proliferation
Mice, Inbred BALB C
rho-Associated Kinases
Liver Neoplasms
Cell Biology
Transfection
Middle Aged
Gene Expression Regulation, Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Guanine nucleotide exchange factor
rhoA GTP-Binding Protein
Rho Guanine Nucleotide Exchange Factors
Signal Transduction
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 374
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....849d72370d14bc8299fb1507b860d2b5