The metastatic promoter DEPDC1B induces epithelial-mesenchymal transition and promotes prostate cancer cell proliferation via Rac1-PAK1 signaling.
The metastatic promoter DEPDC1B induces epithelial-mesenchymal transition and promotes prostate cancer cell proliferation via Rac1-PAK1 signaling.
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转移启动子 DEPDC1B 通过 Rac1-PAK1 信号传导诱导上皮间质转化并促进前列腺癌细胞增殖。
DOI：
10.1002/ctm2.191
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发表时间：
2020-10
影响因子：
10.6
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Li Z;Wang Q;Peng S;Yao K;Chen J;Tao Y;Gao Z;Wang F;Li H;Cai W;Lai Y;Li K;Chen X;Huang H
转移是前列腺癌(Pca)相关死亡的主要原因。上皮-间充质转化(EMT)是癌细胞在转移初期适应和存活的重要特征。因此，有必要明确EMT在转移性前列腺癌(MPCA)中的调控机制，并开发一种新的治疗方法来阻断PCa的转移。在此，我们发现了一个新的前列腺癌转移癌基因，DEP结构域包含1B(DEPDC1B)，它与肿瘤转移状态、高Gleason评分、肿瘤分期和预后不良呈正相关。功能分析显示，DEPDC1B在体外可促进PCa细胞的迁移、侵袭和增殖，在体内可促进肿瘤的转移和生长。机制研究表明，DEPDC1B通过与rac1结合并增强rac1-PAK1通路，诱导EMT并促进细胞增殖。这种DEPDC1B介导的致癌效应可被rac1-GTP抑制剂或rac1基因敲除所逆转。综上所述，我们发现DEPDC1B-rac1-PAK1信号通路可能成为临床干预MPCa的多潜能靶点。提示：1.DEPDC1B与前列腺癌转移、肿瘤分期、Gleason评分、预后不良呈正相关。2.DEPDC1B在体内外促进前列腺癌细胞转移和肿瘤生长。3.DEPDC1B通过增强rac1-PAK1信号通路诱导EMT。4.DEPDC1B通过rac1-PAK1信号通路参与肿瘤的转移和增殖。
Metastasis is the major cause of prostate cancer (PCa)‐related mortality. Epithelial‐mesenchymal transition (EMT) is a vital characteristic feature that empowers cancer cells to adapt and survive at the beginning of metastasis. Therefore, it is essential to identify the regulatory mechanism of EMT in metastatic prostate cancer (mPCa) and to develop a novel therapy to block PCa metastasis. Here, we discovered a novel PCa metastasis oncogene, DEP domain containing 1B (DEPDC1B), which was positively correlated with the metastasis status, high Gleason score, advanced tumor stage, and poor prognosis. Functional assays revealed that DEPDC1B enhanced the migration, invasion, and proliferation of PCa cells in vitro and promoted tumor metastasis and growth in vivo. Mechanistic investigations clarified that DEPDC1B induced EMT and enhanced proliferation by binding to Rac1 and enhancing the Rac1‐PAK1 pathway. This DEPDC1B‐mediated oncogenic effect was reversed by a Rac1‐GTP inhibitor or Rac1 knockdown. In conclusion, we discover that the DEPDC1B‐Rac1‐PAK1 signaling pathway may serve as a multipotent target for clinical intervention in mPCa. Highlights 1. DEPDC1B positively correlates with prostate cancer metastasis, tumor stage, Gleason score, and poor prognosis. 2. DEPDC1B enhances prostate cancer cell metastasis and tumor growth in vitro and in vivo. 3. DEPDC1B enhances the Rac1‐PAK1 signaling pathway to induce EMT. 4. DEPDC1B contributing to metastasis and proliferation through Rac1‐PAK1 signaling.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
3.5
作者：
Balasenthil, S;Barnes, CJ;Kumar, R
通讯作者：
Kumar, R
影响因子：
5.4
作者：
Kelly SP;Anderson WF;Rosenberg PS;Cook MB
通讯作者：
Cook MB
高水平的 DEPDC1B 预测前列腺癌患者的生化无复发生存期较短
影响因子：
2.9
作者：
Bai, Shoumin;Chen, Ting;Huang, Hai
通讯作者：
Huang, Hai
MicroRNA-331-3p 通过 Rac1/PAK1/β-catenin 轴靶向 ErbB2 和 VAV2，抑制非小细胞肺癌中的上皮间质转化
影响因子：
5.7
作者：
Li, Xizhe;Zhu, Jiali;Zhang, Chunfang
通讯作者：
Zhang, Chunfang