title: Androgen receptor enhances cell adhesion and decreases cell migration via modulating β1-integrin-AKT signaling in hepatocellular carcinoma cells.
abstract: The androgen receptor (AR) has been shown to promote the initiation and development of hepatocellular carcinoma (HCC) during the early stage of the disease process and to suppress HCC cell invasion during the later stages of the disease. The mechanisms governing these dual yet opposite roles have yet to be elucidated. Using carcinogen-induced HCC in vivo mouse models and the in vitro human HCC cell line SKhep1, we found that knockout of AR in primary HCC cells led to a decrease in HCC cell focal adhesion capacity compared to cells from wildtype mice. Similar results were obtained after adding functional AR into human HCC SKhep1 cells. Further analysis revealed that the role AR plays in adhesion of HCC cells is governed, at least in part, by its ability to up-regulate β1-integrin and activate the PI3K/AKT pathway. We also found that AR-β1-integrin-mediated cell adhesion suppresses cell migration. Those findings indicate that the AR-β1-integrin-PI3K/AKT signaling pathway might play a role in the bimodal function of AR on cell adhesion and migration at the cellular level.
authors.affiliation: Sex Hormone Research Center, Organ Transplantation Center, and Department of Gastroenterology, China Medical University and Hospital, Taichung 404, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung 404, Taiwan. Electronic address: maverick@mail.cmu.edu.tw.
authors.forename: Wen-Lung
authors.initials: WL
authors.lastname: Ma
authors.affiliation: Sex Hormone Research Center, Organ Transplantation Center, and Department of Gastroenterology, China Medical University and Hospital, Taichung 404, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung 404, Taiwan.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.affiliation: Sex Hormone Research Center, Organ Transplantation Center, and Department of Gastroenterology, China Medical University and Hospital, Taichung 404, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung 404, Taiwan.
authors.forename: Hsueh-Chou
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Sex Hormone Research Center, Organ Transplantation Center, and Department of Gastroenterology, China Medical University and Hospital, Taichung 404, Taiwan.
authors.forename: Pei-Yin
authors.initials: PY
authors.lastname: Liao
authors.affiliation: Sex Hormone Research Center, Organ Transplantation Center, and Department of Gastroenterology, China Medical University and Hospital, Taichung 404, Taiwan; George Whipple Lab for Cancer Research, Departments of Pathology and Urology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: chang@urmc.rochester.edu.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004052:Diethylnitrosamine; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D039564:Integrin alphaV; D019012:Integrin beta1; D011944:Receptors, Androgen; D004052:Diethylnitrosamine; D051057:Proto-Oncogene Proteins c-akt
keywords: Adhesion; Androgen receptor; Hepatocellular carcinoma; Migration