Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models.

Cancer Letters
Fulvio ChiacchieraCristiano Simone

Abstract

We recently demonstrated that p38α is required to maintain colorectal cancer (CRC) metabolism, as its inhibition leads to FoxO3A activation, autophagy, cell death, and tumor growth reduction both in vitro and in vivo. Here we show that inhibition of p38α is followed by TRAIL-mediated activation of caspase-8 and FoxO3A-dependent HER3 upregulation with consequent overactivation of the MEK-ERK1/2 survival pathway. p38α and MEK combined inhibition specifically induces apoptosis by enabling TRAIL signaling propagation through t-Bid and caspase-3, and fosters cell death in CRC cells and preclinical mouse models. Current MEK1-directed pharmacological strategies could thus be exploited, in combination with p38α inhibition, to develop new approaches for CRC treatment.

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Citations

Aug 28, 2015·International Journal of Molecular Medicine·Lirui ZhangHuilian Hou
Apr 1, 2014·IEEE Transactions on Biomedical Circuits and Systems·Maryam Masnadi-ShiraziShankar Subramaniam
Apr 25, 2016·Cellular Signalling·Lucie PekarčíkováJan Šmarda
Oct 22, 2016·Biochimica Et Biophysica Acta·Nathaniel J Robinson, William P Schiemann
Mar 31, 2017·Journal of Cell Communication and Signaling·Zachary SpethHaluk Resat
Aug 12, 2014·World Journal of Gastroenterology : WJG·Valentina GrossiCristiano Simone
Oct 14, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jackie E BaderE Angela Murphy
Apr 14, 2018·Experimental & Molecular Medicine·Yong ZhangMan-Tian Mi
Dec 18, 2018·Frontiers in Immunology·Woo Jae ShinRussell K Pachynski
Sep 7, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Bo YuTianfeng Chen

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