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@article{1344839,
author = {Pekarčíková, Lucie and Knopfová, Lucia and Beneš, Petr and Šmarda, Jan},
article_location = {New York, USA},
article_number = {8},
doi = {http://dx.doi.org/10.1016/j.cellsig.2016.04.007},
keywords = {Colorectal carcinoma; c-Myb; NADPH oxidase; Cell survival; Reactive oxygen species; Signaling pathway},
language = {eng},
issn = {0898-6568},
journal = {Cellular Signalling},
title = {c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells},
volume = {28},
year = {2016}
}
TY - JOUR
ID - 1344839
AU - Pekarčíková, Lucie - Knopfová, Lucia - Beneš, Petr - Šmarda, Jan
PY - 2016
TI - c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells
JF - Cellular Signalling
VL - 28
IS - 8
SP - 924-936
EP - 924-936
PB - Elsevier Science
SN - 08986568
KW - Colorectal carcinoma
KW - c-Myb
KW - NADPH oxidase
KW - Cell survival
KW - Reactive oxygen species
KW - Signaling pathway
N2 - The c-Myb transcription factor is important for maintenance of immature cells of many tissues including colon epithelium. Overexpression of c-Myb occurring in colorectal carcinomas (CRC) as well as in other cancers often marks poor prognosis. However, the molecular mechanism explaining how c-Myb contributes to progression of CRC has not been fully elucidated. To address this point, we investigated the way how c-Myb affects sensitivity of CRC cells to anticancer drugs. Using CRC cell lines expressing exogenous c-myb we show that c-Myb protects CRC cells from the cisplatin-, oxaliplatin-, and doxorubicin-induced apoptosis, elevates reactive oxygen species via up-regulation of NOX1, and sustains the pro-survival p38 MAPK pathway. Using pharmacological inhibitors and gene silencing of p38 and NOX1 we found that these proteins are essential for the protective effect of c-Myb and that NOX1 acts upstream of p38 activation. In addition, our result suggests that transcription of NOX1 is directly controlled by c-Myb and these genes are strongly co-expressed in human tumor tissue of CRC patients. The novel c-Myb/NOX1/p38 signaling axis that protects CRC cells from chemotherapy described in this study could provide a new base for design of future therapies of CRC.
ER -
PEKARČÍKOVÁ, Lucie, Lucia KNOPFOVÁ, Petr BENEŠ a Jan ŠMARDA. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells. \textit{Cellular Signalling}. New York, USA: Elsevier Science, roč.~28, č.~8, s.~924-936. ISSN~0898-6568. doi:10.1016/j.cellsig.2016.04.007. 2016.
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