RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential

Benjamin Van Espen, Htoo Zarni Oo, Colin Collins, Ladan Fazli, Alfredo Molinolo, Kevin Yip, Rabi Murad, Martin Gleave, Ze'ev A. Ronai

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)41-54
Number of pages14
JournalMolecular Cancer Research
Volume22
Issue number1
DOIs
StatePublished - Jan 2024
Externally publishedYes

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