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

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.937

RIV identification code

RIV/00216224:14310/16:00088855

Organization unit

Faculty of Science

DOI

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

UT WoS

000378670900015

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

V originále

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

Citovat

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.

@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.

Detailed Information on Publication Record