NR2F2 controls malignant squamous cell carcinoma state by promoting stemness and invasion and repressing differentiation
| Autor: | Cédric Blanpain, Marie Miglianico, Isabelle Salmon, Erwin Nkusi, Federico Mauri, Sandrine Rorive, Christos Sotiriou, Justine Allard, Jeremy Blondeau, Christine Dubois, Yacine Bareche, Milena Rozzi, Gaëlle Lapouge, Benoit Durdu, Audrey Brisebarre, Jalal Vakili, Corentin Schepkens, Ievgenia Pastushenko, Sophie Golstein, Maylis Raphaël, Floriane Ribeiro, Virginie Moers, Yura Song, Benjamin Drogat |
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| Jazyk: | angličtina |
| Předmět: |
Cancer Research
Epithelial-Mesenchymal Transition Skin Neoplasms Cell Regulator Cell Differentiation Biology medicine.disease Gene Expression Regulation Neoplastic Mice medicine.anatomical_structure Oncology Nuclear receptor In vivo Cancer stem cell embryonic structures Carcinoma medicine Cancer research Skin Squamous Cell Carcinoma Carcinoma Squamous Cell Animals Loss function Neoplastic Processes |
| Zdroj: | Nature Cancer |
| ISSN: | 2662-1347 |
| DOI: | 10.1038/s43018-021-00287-5 |
| Popis: | 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. Blanpain and colleagues identify NR2F2 as a regulator of stemness and invasiveness that promotes tumor renewal and restricts differentiation to sustain squamous cell carcinomas. |
| Databáze: | OpenAIRE |
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