Abstract:
Prostate cancer is the second most commonly diagnosed cancer in men and one of the main leading causes of cancer deaths among men worldwide. Rapid uncontrolled growth and the ability to metastasize to other sites are key hallmarks in cancer development and progression. The Rho family of GTPases and its activators the GTPase-activating proteins (GAPs) are required for regulating cancer cell proliferation and migration. StarD13 is a GAP for Rho GTPases, specifically for RhoA and Cdc42. We have previously shown that StarD13 acts as a tumor suppressor in astrocytoma as well as breast and colorectal cancer. In this study, we performed a functional comparative analysis of StarD13 targets/and or interacting molecules to understand the general role that StarD13 plays in cancers. We then investigated the role of StarD13 in prostate cancer, specifically with regards to cell proliferation and metastasis. Our data highlight the importance of StarD13 in modulating several hallmarks of cancer. Findings from database mining and immunohistochemistry further revealed that StarD13 is underexpressed in prostate cancers consistent with its role as a tumor suppressor. Knocking down StarD13 using siRNA also showed that inhibiting StarD13 increases cancer cell proliferation in 2D and thus confirming its role as a tumor suppressor. Interestingly, we noted that StarD13 depletion increases invasion and matrix degradation of prostate cancer cells but suppresses cell migration in 2D through enhanced adhesion. Altogether, the data presented suggests that StarD13 acts as a tumor suppressor which is also required for promoting prostate cancer cell motility in 2D.
