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

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 i...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536616/
https://www.ncbi.nlm.nih.gov/pubmed/33135357
http://dx.doi.org/10.1002/ctm2.191
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author 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
author_facet 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
author_sort Li, Zean
collection PubMed
description 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.
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spelling pubmed-75366162020-10-09 The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling 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 Clin Transl Med Research Articles 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. John Wiley and Sons Inc. 2020-10-06 /pmc/articles/PMC7536616/ /pubmed/33135357 http://dx.doi.org/10.1002/ctm2.191 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title_full The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title_fullStr The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title_full_unstemmed The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title_short The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
title_sort metastatic promoter depdc1b induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via rac1‐pak1 signaling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536616/
https://www.ncbi.nlm.nih.gov/pubmed/33135357
http://dx.doi.org/10.1002/ctm2.191
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