ARHGAP29 expression may be a novel prognostic factor of cell proliferation and invasion in prostate cancer

Abstract

Yes-associated protein (YAP) is a transcription-coupling factor that plays a central role in the Hippo pathway, and its activation regulates cell proliferation and carcinogenesis. YAP activation has been reported in various malignancies, conferring tumors with migratory and invasive abilities. Several studies have suggested that YAP expression is closely associated with prostate cancer. Furthermore, YAP has been revealed to regulate destabilization of F-actin associated with the cytoskeleton via Rho GTPase-activating protein 29 (ARHGAP29), suggesting that ARHGAP29 is associated with cancer metastasis. In the present study, the functions of ARHGAP29 were examined in four prostate cancer cell lines (22Rv1, LNCaP, DU145 and PC-3) and it was revealed that upregulation of ARHGAP29 in LNCaP and DU145 cells with the lowest expression of ARHGAP29 promoted cell proliferation and invasion. Conversely, ARHGAP29 knockdown in PC-3 cells with its highest expression level significantly reduced cell proliferation and invasion. In addition, immunohistochemistry of specimens from 133 patients who underwent radical prostatectomy was performed to investigate the clinical association between ARHGAP29 expression and prognosis in prostate cancer patients. Multivariate analysis demonstrated that ARHGAP29 was an independent prognostic factor for biochemical progression-free survival (P=0.0123). These findings indicated that ARHGAP29 in prostate cancer may be a potential prognostic biomarker and therapeutic target.