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DEPDC1通过激活前列腺癌中的E2F信号通路促进细胞增殖和肿瘤生长。

DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

作者信息

Huang Lin, Chen Keng, Cai Zhao-Peng, Chen Fu-Chao, Shen Hui-Yong, Zhao Wei-Hua, Yang Song-Jie, Chen Xu-Biao, Tang Guo-Xue, Lin Xi

机构信息

Department of Orthopedics, Memorial Hospital of Sun Yat-sen University, Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China.

Department of Orthopedics, Memorial Hospital of Sun Yat-sen University, Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China.

出版信息

Biochem Biophys Res Commun. 2017 Aug 26;490(3):707-712. doi: 10.1016/j.bbrc.2017.06.105. Epub 2017 Jun 19.

Abstract

DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease.

摘要

含DEP结构域蛋白1(DEPDC1)最近被报道在多种人类癌症中过表达;然而,DEPDC1在前列腺癌中的作用仍有待研究。在此,我们发现DEPDC1 mRNA和蛋白表达水平在前列腺癌组织和细胞系中显著升高。DEPDC1的过表达促进了细胞增殖,但DEPDC1的缺失通过调节G1-S期细胞周期转换抑制了细胞增殖。重要的是,我们发现DEPDC1对于前列腺癌细胞在体内的肿瘤生长和骨转移形成至关重要。最后,我们证明DEPDC1与E2F1相互作用并增加其转录活性,导致前列腺癌细胞中E2F信号的过度激活。我们的研究结果揭示了DEPDC1通过激活E2F信号在前列腺癌进展中的致癌作用,并表明DEPDC1可能是针对该疾病的潜在治疗靶点。

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