| Autor: |
de Carné Trécesson, Sophie, Souazé, Frédérique, Basseville, Agnès, Bernard, Anne-Charlotte, Pécot, Jessie, Lopez, Jonathan, Bessou, Margaux, Sarosiek, Kristopher A., Letai, Anthony, Barillé-Nion, Sophie, Valo, Isabelle, Coqueret, Olivier, Guette, Catherine, Campone, Mario, Gautier, Fabien, Juin, Philippe Paul |
| Předmět: |
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| Zdroj: |
Nature Communications; 10/24/2017, Vol. 8 Issue 1, p1-11, 11p |
| Abstrakt: |
In tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-XL is thought to result from the counter selection of sensitive, low expresser clones during progression and/or initial treatment. We herein show that BCL-XL expression is selectively advantageous to cancer cell populations even in the absence of proapoptotic pressure. In transformed human mammary epithelial cells BCL-XL 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-XL modulation of RAS-induced self-renewal, and during which apoptotic resistance is not necessarily the directly selected trait. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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