Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial-mesenchymal transitions and facilitates early metastasis.

Autor: Francart ME; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Vanwynsberghe AM; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Lambert J; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Bourcy M; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Genna A; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Ancel J; Hôpital Maison Blanche, Service de pneumologie, CHU de Reims, 51092, Reims, France.; INSERM, P3Cell UMR-S1250, SFR CAP-SANTE, Université de Reims Champagne-Ardenne, 51097, Reims, France., Perez-Boza J; GIGA-Cancer, Molecular Angiogenesis Laboratory, University of Liège, Liège, Belgium., Noël A; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium., Birembaut P; INSERM, P3Cell UMR-S1250, SFR CAP-SANTE, Université de Reims Champagne-Ardenne, 51097, Reims, France., Struman I; GIGA-Cancer, Molecular Angiogenesis Laboratory, University of Liège, Liège, Belgium., Polette M; INSERM, P3Cell UMR-S1250, SFR CAP-SANTE, Université de Reims Champagne-Ardenne, 51097, Reims, France.; Hôpital Maison Blanche, Laboratoire de pathologie, CHU de Reims, 51092, Reims, France., Gilles C; GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium. cgilles@uliege.be.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2020 Apr; Vol. 39 (18), pp. 3680-3692. Date of Electronic Publication: 2020 Mar 10.
DOI: 10.1038/s41388-020-1244-1
Abstrakt: Epithelial-mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3'-UTR-luciferase reporter vector assays implicated the 3'-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3'UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.
Databáze: MEDLINE
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