PMID- 37831068 OWN - NLM STAT- MEDLINE DCOM- 20240103 LR - 20240206 IS - 1557-3125 (Electronic) IS - 1541-7786 (Print) IS - 1541-7786 (Linking) VI - 22 IP - 1 DP - 2024 Jan 2 TI - RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential. PG - 41-54 LID - 10.1158/1541-7786.MCR-23-0512 [doi] AB - RNF185 is a RING finger domain-containing ubiquitin ligase implicated in ER-associated degradation. Prostate tumor patient data analysis revealed a negative correlation between RNF185 expression and prostate cancer progression and metastasis. Likewise, several prostate cancer cell lines exhibited greater migration and invasion capabilities in culture upon RNF185 depletion. Subcutaneous inoculation of mouse prostate cancer MPC3 cells stably expressing short hairpin RNA against RNF185 into mice resulted in larger tumors and more frequent lung metastases. RNA-sequencing and Ingenuity Pathway Analysis identified wound-healing and cellular movement among the most significant pathways upregulated in RNF185-depleted lines, compared with control prostate cancer cells. Gene Set Enrichment Analyses performed in samples from patients harboring low RNF185 expression and in RNF185-depleted lines confirmed the deregulation of genes implicated in epithelial-to-mesenchymal transition. Among those, COL3A1 was identified as the primary mediator of RNF185's ability to impact migration phenotypes. Correspondingly, enhanced migration and metastasis of RNF185 knockdown (KD) prostate cancer cells were attenuated upon co-inhibition of COL3A1. Our results identify RNF185 as a gatekeeper of prostate cancer metastasis, partly via its control of COL3A1 availability. IMPLICATIONS: RNF185 is identified as an important regulator of prostate cancer migration and metastasis, in part due to its regulation of COL3A1. Both RNF185 and COL3A1 may serve as novel markers for prostate tumors. CI - (c)2023 American Association for Cancer Research. FAU - Van Espen, Benjamin AU - Van Espen B AUID- ORCID: 0000-0003-1587-4942 AD - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. FAU - Oo, Htoo Zarni AU - Oo HZ AUID- ORCID: 0009-0009-8514-2713 AD - Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. FAU - Collins, Colin AU - Collins C AUID- ORCID: 0000-0001-6148-6110 AD - Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. FAU - Fazli, Ladan AU - Fazli L AUID- ORCID: 0009-0005-0731-0583 AD - Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. FAU - Molinolo, Alfredo AU - Molinolo A AUID- ORCID: 0000-0001-8412-2889 AD - Department of Pathology, University of California San Diego, La Jolla, California. FAU - Yip, Kevin AU - Yip K AUID- ORCID: 0000-0001-5516-9944 AD - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. FAU - Murad, Rabi AU - Murad R AUID- ORCID: 0009-0004-5297-8307 AD - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. FAU - Gleave, Martin AU - Gleave M AUID- ORCID: 0000-0003-4235-0167 AD - Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. FAU - Ronai, Ze'ev A AU - Ronai ZA AUID- ORCID: 0000-0002-3859-0400 AD - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. LA - eng GR - P30 CA030199/CA/NCI NIH HHS/United States GR - R35 CA197465/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Mol Cancer Res JT - Molecular cancer research : MCR JID - 101150042 RN - 0 (RNA, Small Interfering) RN - 0 (COL3A1 protein, human) RN - 0 (Collagen Type III) RN - EC 2.3.2.27 (RNF185 protein, human) RN - 0 (Mitochondrial Proteins) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM UOF - bioRxiv. 2023 Jul 01;:. PMID: 37425866 MH - Male MH - Humans MH - Mice MH - Animals MH - *Prostatic Neoplasms/pathology MH - Prostate/pathology MH - Cell Movement/genetics MH - Epithelial-Mesenchymal Transition MH - RNA, Small Interfering MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic MH - Collagen Type III/genetics/metabolism MH - Mitochondrial Proteins/genetics MH - Ubiquitin-Protein Ligases/genetics/metabolism PMC - PMC10841372 MID - NIHMS1939064 EDAT- 2023/10/13 12:42 MHDA- 2024/01/03 09:43 PMCR- 2024/07/02 CRDT- 2023/10/13 11:04 PHST- 2023/06/29 00:00 [received] PHST- 2023/09/19 00:00 [revised] PHST- 2023/10/11 00:00 [accepted] PHST- 2024/07/02 00:00 [pmc-release] PHST- 2024/01/03 09:43 [medline] PHST- 2023/10/13 12:42 [pubmed] PHST- 2023/10/13 11:04 [entrez] AID - 729588 [pii] AID - 10.1158/1541-7786.MCR-23-0512 [doi] PST - ppublish SO - Mol Cancer Res. 2024 Jan 2;22(1):41-54. doi: 10.1158/1541-7786.MCR-23-0512.