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Title: | De novo MYC addiction as an adaptive response of cancer cells to CDK4/6 inhibition |
Author: | Tarrado Castellarnau, Míriam Neus Atauri Carulla, Ramón de Tarragó-Celada, Josep Perarnau, Jordi Yuneva, Mariia Thomson, Timothy M. Cascante i Serratosa, Marta |
Keywords: | Càncer Transducció de senyal cel·lular Cancer Cellular signal transduction |
Issue Date: | 4-Oct-2017 |
Publisher: | EMBO Press |
Abstract: | Cyclin‐dependent kinases (CDK) are rational cancer therapeutic targets fraught with the development of acquired resistance by tumor cells. Through metabolic and transcriptomic analyses, we show that the inhibition of CDK4/6 leads to a metabolic reprogramming associated with gene networks orchestrated by the MYC transcription factor. Upon inhibition of CDK4/6, an accumulation of MYC protein ensues which explains an increased glutamine metabolism, activation of the mTOR pathway and blunting of HIF‐1α‐mediated responses to hypoxia. These MYC‐driven adaptations to CDK4/6 inhibition render cancer cells highly sensitive to inhibitors of MYC, glutaminase or mTOR and to hypoxia, demonstrating that metabolic adaptations to antiproliferative drugs unveil new vulnerabilities that can be exploited to overcome acquired drug tolerance and resistance by cancer cells. |
Note: | Reproducció del document publicat a: https://doi.org/10.15252/msb.20167321 |
It is part of: | Molecular Systems Biology, 2017, vol. 13, num. 10, p. 940 |
URI: | http://hdl.handle.net/2445/122636 |
Related resource: | https://doi.org/10.15252/msb.20167321 |
ISSN: | 1744-4292 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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