Regulation of the RhoA/ROCK/AKT/β-catenin pathway by arginine-specific ADP-ribosytransferases 1 promotes migration and epithelial-mesenchymal transition in colon carcinoma.
Arginine-specific ADP-ribosytransferases 1 (ART1) is able to modify the arginine of specific proteins by mono-ADP-ribosylation. We previously reported that the expression of ART1 in human colon adenocarcinoma tissues was higher than in adjacent tissues. Herein, we primarily revealed that ART1 could regulate the epithelial-mesenchymal transition (EMT) and, therefore, the development of colon carcinoma. In CT26 cells, which overexpressed ART1 by lentiviral transfection, the following were promoted: alterations of spindle-like non-polarization, expression of EMT inducers and mesenchymal markers, migration, invasion and adhesion. However, epithelial marker expression was decreased. Correspondingly, knockdown of ART1 in CT26 cells had the opposite effects. The effect of ART1 on EMT and carcinoma metastasis was also verified in a liver metastasis model of BALB/c mice. To further explore the molecular mechanism of ART1 in EMT, CT26 cells were treated with several specific inhibitors and gene silencing. Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/β-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma.
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Guang-Lin
GL
Song
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Cong-Cong
CC
Jin
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Wei
W
Zhao
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Yi
Y
Tang
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Ya-Lan
YL
Wang
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Ming
M
Li
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Ming
M
Xiao
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Xian
X
Li
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Qing-Shu
QS
Li
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Xiao
X
Lin
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Wen-Wen
WW
Chen
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Jing
J
Kuang
D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D016086:Lentivirus; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics; D054460:rho-Associated Kinases / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics
D058851:GPI-Linked Proteins; D051176:beta Catenin; D001120:Arginine; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; D051058:Oncogene Protein v-akt; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein