BCL-X L directly modulates RAS signalling to favour cancer cell stemness.

Autor:	Carné Trécesson S; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France.; Oncogene Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Souazé F; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France., Basseville A; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France., Bernard AC; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France., Pécot J; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France., Lopez J; Service de Biochimie et Biologie moléculaire-Centre Hospitalier Lyon Sud, Faculté de Médecine Lyon Sud-Université Lyon 1, Centre de Recherche en Cancérologie de Lyon-INSERM U1052 CNRS U5286, Lyon, 69003, France., Bessou M; Service de Biochimie et Biologie moléculaire-Centre Hospitalier Lyon Sud, Faculté de Médecine Lyon Sud-Université Lyon 1, Centre de Recherche en Cancérologie de Lyon-INSERM U1052 CNRS U5286, Lyon, 69003, France., Sarosiek KA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA., Letai A; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA., Barillé-Nion S; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France., Valo I; Biopathology Department, ICO - Centre de Lutte contre le Cancer Paul Papin, 15 rue André Boquel, Angers, France.; Team 12 'Targeted Therapies and Tumor Escape in Colorectal Cancer', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - Centre de Lutte contre le Cancer Paul Papin, 15 rue André Boquel, Angers, 49055, France., Coqueret O; Team 12 'Targeted Therapies and Tumor Escape in Colorectal Cancer', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - Centre de Lutte contre le Cancer Paul Papin, 15 rue André Boquel, Angers, 49055, France.; ICO site Paul Papin, 15 rue André Boquel, Angers, 49055, France., Guette C; Team 12 'Targeted Therapies and Tumor Escape in Colorectal Cancer', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - Centre de Lutte contre le Cancer Paul Papin, 15 rue André Boquel, Angers, 49055, France.; ICO site Paul Papin, 15 rue André Boquel, Angers, 49055, France., Campone M; ICO site René Gauducheau, Boulevard Jacques Monod, Saint Herblain, 44805, France., Gautier F; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France.; ICO site René Gauducheau, Boulevard Jacques Monod, Saint Herblain, 44805, France., Juin PP; Team 8 'Stress adaptation and tumor escape', CRCINA - Institut de Recherche en Santé de l'Université de Nantes-Angers - IRT, BP 70721, 8 quai Moncousu, Nantes, 44007, France. philippe.juin@univ-nantes.fr.; ICO site René Gauducheau, Boulevard Jacques Monod, Saint Herblain, 44805, France. philippe.juin@univ-nantes.fr.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Oct 24; Vol. 8 (1), pp. 1123. Date of Electronic Publication: 2017 Oct 24.
DOI:	10.1038/s41467-017-01079-1
Abstrakt:	In tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-X L is thought to result from the counter selection of sensitive, low expresser clones during progression and/or initial treatment. We herein show that BCL-X L expression is selectively advantageous to cancer cell populations even in the absence of pro-apoptotic pressure. In transformed human mammary epithelial cells BCL-X L favours full activation of signalling downstream of constitutively active RAS with which it interacts in a BH4-dependent manner. Comparative proteomic analysis and functional assays indicate that this is critical for RAS-induced expression of stemness regulators and maintenance of a cancer initiating cell (CIC) phenotype. Resistant cancer cells thus arise from a positive selection driven by BCL-X L modulation of RAS-induced self-renewal, and during which apoptotic resistance is not necessarily the directly selected trait.
Databáze:	MEDLINE
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