Androgen receptor enhances cell adhesion and decreases cell migration via modulating β1-integrin-AKT signaling in hepatocellular carcinoma cells

• This paper explained in cellular level why AR promotes cancer growth, and suppresses metastasis.
• AR signal promote cell focal adhesion through β1-integrin expression.
• AR signal suppress cell migration also through β1-integrin expression.
• The AR-β1-integrin pathway could enhance activation of PI3K/AKT signaling.

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.