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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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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. |
format | Online Article Text |
id | pubmed-7536616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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