The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling

• Published in: Clinical and translational medicine Vol. 10; no. 6; pp. e191 - n/a
• Main Authors: Li, Zean, Wang, Qiong, Peng, Shirong, Yao, Kai, Chen, Junxiu, Tao, Yiran, Gao, Ze, Wang, Fen, Li, Hui, Cai, Wenli, Lai, Yiming, Li, Kaiwen, Chen, Xu, Huang, Hai
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01-10-2020; Wiley
• Subjects: DEPDC1B; EMT; prostate cancer; Rac1; DEPDC1B; prostate cancer; Rac1; EMT
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.191

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.