PEKARČÍKOVÁ, Lucie, Lucia KNOPFOVÁ, Petr BENEŠ and Jan ŠMARDA. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells. Cellular Signalling. New York, USA: Elsevier Science, 2016, vol. 28, No 8, p. 924-936. ISSN 0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2016.04.007. |
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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 and Jan ŠMARDA. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells. \textit{Cellular Signalling}. New York, USA: Elsevier Science, 2016, vol.~28, No~8, p.~924-936. ISSN~0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2016.04.007.
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