The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.191 |
| _version_ | 1819297243668152320 |
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| author | Zean Li Qiong Wang Shirong Peng Kai Yao Junxiu Chen Yiran Tao Ze Gao Fen Wang Hui Li Wenli Cai Yiming Lai Kaiwen Li Xu Chen Hai Huang |
| author_facet | Zean Li Qiong Wang Shirong Peng Kai Yao Junxiu Chen Yiran Tao Ze Gao Fen Wang Hui Li Wenli Cai Yiming Lai Kaiwen Li Xu Chen Hai Huang |
| author_sort | Zean Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-24T05:10:55Z |
| format | Article |
| id | doaj.art-2a9e7357439a41c6a4d1811e7e562f4b |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-24T05:10:55Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-2a9e7357439a41c6a4d1811e7e562f4b2022-12-21T17:13:41ZengWileyClinical and Translational Medicine2001-13262020-10-01106n/an/a10.1002/ctm2.191The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signalingZean Li0Qiong Wang1Shirong Peng2Kai Yao3Junxiu Chen4Yiran Tao5Ze Gao6Fen Wang7Hui Li8Wenli Cai9Yiming Lai10Kaiwen Li11Xu Chen12Hai Huang13Department of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaCenter for Cancer and Stem Cell Biology Texas A&M Health Science Center Institute of Biosciences and Technology Houston TexasDepartment of Pathology School of Medicine University of Virginia Charlottesville VirginiaDepartment of Radiology Massachusetts General Hospital Harvard Medical School Boston MassachusettsDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaDepartment of Urology Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University Guangzhou Guangdong P. R. ChinaAbstract 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.https://doi.org/10.1002/ctm2.191DEPDC1BEMTprostate cancerRac1 |
| spellingShingle | Zean Li Qiong Wang Shirong Peng Kai Yao Junxiu Chen Yiran Tao Ze Gao Fen Wang Hui Li Wenli Cai Yiming Lai Kaiwen Li Xu Chen Hai Huang The metastatic promoter DEPDC1B induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK1 signaling Clinical and Translational Medicine DEPDC1B EMT prostate cancer Rac1 |
| 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 | DEPDC1B EMT prostate cancer Rac1 |
| url | https://doi.org/10.1002/ctm2.191 |
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