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Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated G alpha s-cAMP pathway and AR-YAP1 axis
DC Field | Value | Language |
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dc.contributor.author | Kim, Ji Won | - |
dc.contributor.author | Park, Miso | - |
dc.contributor.author | Kim, Suntae | - |
dc.contributor.author | Lim, Sung Chul | - |
dc.contributor.author | Kim, Hyung Shik | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.date.accessioned | 2022-05-23T05:19:15Z | - |
dc.date.available | 2022-05-23T05:19:15Z | - |
dc.date.created | 2021-12-28 | - |
dc.date.issued | 2021-11 | - |
dc.identifier.citation | Cell and Bioscience, Vol.11 No.1, p. 191 | - |
dc.identifier.issn | 2045-3701 | - |
dc.identifier.uri | https://hdl.handle.net/10371/180064 | - |
dc.description.abstract | Background: Gonadotropin-releasing hormone receptor (GnRHR) transmits its signal via two major G alpha-proteins, primarily G alpha q and G alpha i. However, the precise mechanism underlying the functions of G alpha s signal in prostate cancer cells is still unclear. We have previously identified that GV1001, a fragment of the human telomerase reverse transcriptase, functions as a biased GnRHR ligand to selectively stimulate the G alpha s/cAMP pathway. Here, we tried to reveal the potential mechanisms of which GV1001-stimulated G alpha s-cAMP signaling pathway reduces the migration and metastasis of prostate cancer (PCa) cells. Methods: The expression of epithelial-mesenchymal transition (EMT)-related genes was measured by western-blotting and spheroid formation on ultra-low attachment plate was detected after GV1001 treatment. In vivo Spleen-liver metastasis mouse model was used to explore the inhibitory effect of GV1001 on metastatic ability of PCa and the transwell migration assay was performed to identify whether GV1001 had a suppressive effect on cell migration in vitro. In order to demonstrate the interaction between androgen receptor (AR) and YAP1, co-immunoprecipitation (co-IP), immunofluorescence (IF) staining, chromatin immunoprecipitation (ChIP) were performed in LNCaP cells with and without GV1001 treatment. Results: GV1001 inhibited expression of EMT-related genes and spheroid formation. GV1001 also suppressed in vivo spleen-liver metastasis of LNCaP cells as well as cell migration in vitro. GV1001 enhanced the phosphorylation of AR and transcription activity of androgen response element reporter gene through cAMP/protein kinase A pathway. Moreover, GV1001 increased Ser-127 phosphorylation of YAP1 and its ubiquitination, and subsequently decreased the levels of AR-YAP1 binding in the promoter region of the CTGF gene. In contrast, both protein and mRNA levels of NKX3.1 known for tumor suppressor gene and AR-coregulator were upregulated by GV1001 in LNCaP cells. YAP1 knockout using CRISPR/Cas9 significantly suppressed the migration ability of LNCaP cells, and GV1001 did not affect the cell migration of YAP1-deficient LNCaP cells. On the contrary, cell migration was more potentiated in LNCaP cells overexpressing YAP5SA, a constitutively active form of YAP1, which was not changed by GV1001 treatment. Conclusions: Overall, this study reveals an essential role of AR-YAP1 in the regulation of PCa cell migration, and provides evidence that GV1001 could be a novel GnRHR ligand to inhibit metastasis of PCa via the G alpha s/cAMP pathway. | - |
dc.language | 영어 | - |
dc.publisher | Society of Chinese Bioscientists in America | - |
dc.title | Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated G alpha s-cAMP pathway and AR-YAP1 axis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1186/s13578-021-00704-3 | - |
dc.citation.journaltitle | Cell and Bioscience | - |
dc.identifier.wosid | 000715191100001 | - |
dc.identifier.scopusid | 2-s2.0-85118694161 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 191 | - |
dc.citation.volume | 11 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kang, Keon Wook | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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