Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan.
Center for Regenerative Medicine, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan.
Oncol Rep. 2020 Dec;44(6):2735-2745. doi: 10.3892/or.2020.7811. Epub 2020 Oct 15.
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.
Yes 相关蛋白 (YAP) 是 Hippo 通路中的一个转录偶联因子,在细胞增殖和致癌作用中发挥核心作用。YAP 的激活已在各种恶性肿瘤中报道,赋予肿瘤迁移和侵袭能力。几项研究表明,YAP 表达与前列腺癌密切相关。此外,已经揭示 YAP 通过 Rho GTPase 激活蛋白 29 (ARHGAP29) 调节与细胞骨架相关的 F-肌动蛋白的不稳定性,表明 ARHGAP29 与癌症转移有关。在本研究中,在四种前列腺癌细胞系(22Rv1、LNCaP、DU145 和 PC-3)中检查了 ARHGAP29 的功能,结果表明在 ARHGAP29 表达最低的 LNCaP 和 DU145 细胞中上调 ARHGAP29 促进了细胞增殖和侵袭。相反,在 ARHGAP29 表达最高的 PC-3 细胞中敲低 ARHGAP29 显著降低了细胞增殖和侵袭。此外,对接受根治性前列腺切除术的 133 名患者的标本进行了免疫组织化学检查,以研究 ARHGAP29 表达与前列腺癌患者预后之间的临床关联。多变量分析表明,ARHGAP29 是生化无进展生存的独立预后因素 (P=0.0123)。这些发现表明,前列腺癌中的 ARHGAP29 可能是一个潜在的预后生物标志物和治疗靶点。