@article{739bb062d1f54c0fa373d7c71d9ba5f3,
title = "Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models",
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.",
keywords = "Animal models, Cell death, Colorectal cancer, ERK, P38",
author = "Fulvio Chiacchiera and Valentina Grossi and Marianna Cappellari and Alessia Peserico and Marta Simonatto and Aldo Germani and Silvana Russo and Moyer, {Mary P.} and Nicoletta Resta and Stefania Murzilli and Cristiano Simone",
note = "Funding Information: We thank Dr. Francesco Paolo Jori for his helpful discussion and editorial assistance, Prof. Bert Vogelstein for kindly providing Hct-116 wt and Bax null cells, Dr. Francesca De Marchi for the anti-LC3 antibody, MT Ciencioni and Dr. Giovanna Forte for technical assistance. Dr. Chiacchiera is supported by a FIRC fellowship, Dr. Grossi by a {\textquoteleft}Fondazione Negri Sud{\textquoteright} fellowship. This work was partially supported by a {\textquoteleft}My First Grant 2007{\textquoteright} and an {\textquoteleft}Investigator Grant 2010{\textquoteright} (IG10177) (to Dr. Simone) from the Italian Association for Cancer Research AIRC. ",
year = "2012",
month = nov,
day = "1",
doi = "10.1016/j.canlet.2012.05.006",
language = "English (US)",
volume = "324",
pages = "98--108",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",
}