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

J 2016

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

PEKARČÍKOVÁ, Lucie; Lucia KNOPFOVÁ; Petr BENEŠ and Jan ŠMARDA

Basic information

Original name

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

Name in Czech

c-Myb řídí přežívání buněk kolorektálního karcinomu prostřednictvím NOX1/p38

Authors

PEKARČÍKOVÁ, Lucie (203 Czech Republic, belonging to the institution); Lucia KNOPFOVÁ (203 Czech Republic, belonging to the institution); Petr BENEŠ (203 Czech Republic, belonging to the institution) and Jan ŠMARDA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cellular Signalling, New York, USA, Elsevier Science, 2016, 0898-6568

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

Impact factor

Impact factor: 3.937

RIV identification code

RIV/00216224:14310/16:00088855

Organization unit

Faculty of Science

DOI

https://doi.org/10.1016/j.cellsig.2016.04.007

UT WoS

000378670900015

EID Scopus

2-s2.0-84966389725

Keywords (in Czech)

kolorektální karcinom; c-Myb; NADPH oxidáza; přežívání buněk; reaktivní kyslíkové radikály; signální dráha

Keywords in English

Colorectal carcinoma; c-Myb; NADPH oxidase; Cell survival; Reactive oxygen species; Signaling pathway

Abstract

In the original language

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.

Links

NT13441, research and development project

Name: Exprese proteinů rodiny Myb v adenokarcinomech tlustého střeva a vztah k jejich metastatickému potenciálu

Cite

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://doi.org/10.1016/j.cellsig.2016.04.007.

@article{1344839,
   author = {Pekarčíková, Lucie and Knopfová, Lucia and Beneš, Petr and Šmarda, Jan},
   article_location = {New York, USA},
   article_number = {8},
   doi = {https://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://doi.org/10.1016/j.cellsig.2016.04.007.

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