Back to Search
Start Over
BCL-XL directly modulates RAS signalling to favour cancer cell stemnessa.
- Source :
- Nature Communications; 10/24/2017, Vol. 8 Issue 1, p1-11, 11p
- Publication Year :
- 2017
-
Abstract
- In tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-X<subscript>L</subscript> 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<subscript>L</subscript> expression is selectively advantageous to cancer cell populations even in the absence of proapoptotic pressure. In transformed human mammary epithelial cells BCL-X<subscript>L</subscript> 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<subscript>L</subscript> modulation of RAS-induced self-renewal, and during which apoptotic resistance is not necessarily the directly selected trait. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 138016339
- Full Text :
- https://doi.org/10.1038/s41467-017-01079-1