c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells

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Authors

PEKARČÍKOVÁ Lucie KNOPFOVÁ Lucia BENEŠ Petr ŠMARDA Jan

Year of publication 2016
Type Article in Periodical
Magazine / Source Cellular Signalling
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1016/j.cellsig.2016.04.007
Field Genetics and molecular biology
Keywords Colorectal carcinoma; c-Myb; NADPH oxidase; Cell survival; Reactive oxygen species; Signaling pathway
Description 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.
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