NR2F2 controls malignant squamous cell carcinoma state by promoting stemness and invasion and repressing differentiation.

Autor: Mauri F; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Schepkens C; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Lapouge G; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Drogat B; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Song Y; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Pastushenko I; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Rorive S; Centre Universitaire Inter Régional d'Expertise en Anatomie Pathologique Hospitalière (CurePath), Jumet, Belgium.; DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), Gosselies, Belgium.; Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium., Blondeau J; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Golstein S; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Bareche Y; Breast Cancer Translational Research Laboratory, J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Miglianico M; ChromaCure SA, Grandbonpré 11/5, Mont-Saint-Guibert, Belgium., Nkusi E; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Rozzi M; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Moers V; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Brisebarre A; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Raphaël M; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Dubois C; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Allard J; DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), Gosselies, Belgium., Durdu B; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Ribeiro F; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium., Sotiriou C; Breast Cancer Translational Research Laboratory, J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Salmon I; Centre Universitaire Inter Régional d'Expertise en Anatomie Pathologique Hospitalière (CurePath), Jumet, Belgium.; DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), Gosselies, Belgium.; Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium., Vakili J; ChromaCure SA, Grandbonpré 11/5, Mont-Saint-Guibert, Belgium., Blanpain C; Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium. Cedric.Blanpain@ulb.be.; WELBIO, Université Libre de Bruxelles (ULB), Bruxelles, Belgium. Cedric.Blanpain@ulb.be.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2021 Nov; Vol. 2 (11), pp. 1152-1169. Date of Electronic Publication: 2021 Nov 22.
DOI: 10.1038/s43018-021-00287-5
Abstrakt: The nongenetic mechanisms required to sustain malignant tumor state are poorly understood. During the transition from benign tumors to malignant carcinoma, tumor cells need to repress differentiation and acquire invasive features. Using transcriptional profiling of cancer stem cells from benign tumors and malignant skin squamous cell carcinoma (SCC), we identified the nuclear receptor NR2F2 as uniquely expressed in malignant SCC. Using genetic gain of function and loss of function in vivo, we show that NR2F2 is essential for promoting the malignant tumor state by controlling tumor stemness and maintenance in mouse and human SCC. We demonstrate that NR2F2 promotes tumor cell proliferation, epithelial-mesenchymal transition and invasive features, while repressing tumor differentiation and immune cell infiltration by regulating a common transcriptional program in mouse and human SCCs. Altogether, we identify NR2F2 as a key regulator of malignant cancer stem cell functions that promotes tumor renewal and restricts differentiation to sustain a malignant tumor state.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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