Opposite regulation of MDM2 and MDMX expression in acquisition
of mesenchymal phenotype in benign and cancer cells

J 2015

Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells

SLABÁKOVÁ, Eva, G. KHARAISHVILI, Monika SMĚJOVÁ, Zuzana PERNICOVÁ, Tereza SUCHÁNKOVÁ et. al.

Basic information

Original name

Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells

Authors

SLABÁKOVÁ, Eva (203 Czech Republic, belonging to the institution), G. KHARAISHVILI (268 Georgia), Monika SMĚJOVÁ (203 Czech Republic, belonging to the institution), Zuzana PERNICOVÁ (203 Czech Republic), Tereza SUCHÁNKOVÁ (203 Czech Republic), Ján REMŠÍK (703 Slovakia, belonging to the institution), Stanislav LERCH (203 Czech Republic, belonging to the institution), Nicol STRAKOVÁ (203 Czech Republic, belonging to the institution), Jan BOUCHAL (203 Czech Republic), Milan KRÁL (203 Czech Republic), Z. CULIG (40 Austria), Alois KOZUBÍK (203 Czech Republic, belonging to the institution) and Karel SOUČEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Oncotarget, Albany, Impact Journals, 2015, 1949-2553

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: 5.008

RIV identification code

RIV/00216224:14310/15:00100428

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.18632/oncotarget.5392

UT WoS

000366111900087

Keywords in English

epithelial-mesenchymal transition; MDM2/MDMX; SNAI2/SLUG; TWIST; prostate/breast cancer

Abstract

V originále

Plasticity of cancer cells, manifested by transitions between epithelial and mesenchymal phenotypes, represents a challenging issue in the treatment of neoplasias. Both epithelial-mesenchymal transition (EMT) and mesenchymalepithelial transition (MET) are implicated in the processes of metastasis formation and acquisition of stem cell-like properties. Mouse double minute (MDM) 2 and MDMX are important players in cancer progression, as they act as regulators of p53, but their function in EMT and metastasis may be contradictory. Here, we show that the EMT phenotype in multiple cellular models and in clinical prostate and breast cancer samples is associated with a decrease in MDM2 and increase in MDMX expression. Modulation of EMT-accompanying changes in MDM2 expression in benign and transformed prostate epithelial cells influences their migration capacity and sensitivity to docetaxel. Analysis of putative mechanisms of MDM2 expression control demonstrates that in the context of defective p53 function, MDM2 expression is regulated by EMT-inducing transcription factors Slug and Twist. These results provide an alternative context-specific role of MDM2 in EMT, cell migration, metastasis, and therapy resistance.

Citovat

SLABÁKOVÁ, Eva, G. KHARAISHVILI, Monika SMĚJOVÁ, Zuzana PERNICOVÁ, Tereza SUCHÁNKOVÁ, Ján REMŠÍK, Stanislav LERCH, Nicol STRAKOVÁ, Jan BOUCHAL, Milan KRÁL, Z. CULIG, Alois KOZUBÍK and Karel SOUČEK. Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells. Oncotarget. Albany: Impact Journals, 2015, vol. 6, No 34, p. 36156-36171. ISSN 1949-2553. Available from: https://dx.doi.org/10.18632/oncotarget.5392.

@article{1411858,
   author = {Slabáková, Eva and Kharaishvili, G. and Smějová, Monika and Pernicová, Zuzana and Suchánková, Tereza and Remšík, Ján and Lerch, Stanislav and Straková, Nicol and Bouchal, Jan and Král, Milan and Culig, Z. and Kozubík, Alois and Souček, Karel},
   article_location = {Albany},
   article_number = {34},
   doi = {http://dx.doi.org/10.18632/oncotarget.5392},
   keywords = {epithelial-mesenchymal transition; MDM2/MDMX; SNAI2/SLUG; TWIST; prostate/breast cancer},
   language = {eng},
   issn = {1949-2553},
   journal = {Oncotarget},
   title = {Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells},
   volume = {6},
   year = {2015}
}

TY  - JOUR
ID  - 1411858
AU  - Slabáková, Eva - Kharaishvili, G. - Smějová, Monika - Pernicová, Zuzana - Suchánková, Tereza - Remšík, Ján - Lerch, Stanislav - Straková, Nicol - Bouchal, Jan - Král, Milan - Culig, Z. - Kozubík, Alois - Souček, Karel
PY  - 2015
TI  - Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells
JF  - Oncotarget
VL  - 6
IS  - 34
SP  - 36156-36171
EP  - 36156-36171
PB  - Impact Journals
SN  - 19492553
KW  - epithelial-mesenchymal transition
KW  - MDM2/MDMX
KW  - SNAI2/SLUG
KW  - TWIST
KW  - prostate/breast cancer
N2  - Plasticity of cancer cells, manifested by transitions between epithelial and mesenchymal phenotypes, represents a challenging issue in the treatment of neoplasias. Both epithelial-mesenchymal transition (EMT) and mesenchymalepithelial transition (MET) are implicated in the processes of metastasis formation and acquisition of stem cell-like properties. Mouse double minute (MDM) 2 and MDMX are important players in cancer progression, as they act as regulators of p53, but their function in EMT and metastasis may be contradictory. Here, we show that the EMT phenotype in multiple cellular models and in clinical prostate and breast cancer samples is associated with a decrease in MDM2 and increase in MDMX expression. Modulation of EMT-accompanying changes in MDM2 expression in benign and transformed prostate epithelial cells influences their migration capacity and sensitivity to docetaxel. Analysis of putative mechanisms of MDM2 expression control demonstrates that in the context of defective p53 function, MDM2 expression is regulated by EMT-inducing transcription factors Slug and Twist. These results provide an alternative context-specific role of MDM2 in EMT, cell migration, metastasis, and therapy resistance.
ER  -

SLABÁKOVÁ, Eva, G. KHARAISHVILI, Monika SMĚJOVÁ, Zuzana PERNICOVÁ, Tereza SUCHÁNKOVÁ, Ján REMŠÍK, Stanislav LERCH, Nicol STRAKOVÁ, Jan BOUCHAL, Milan KRÁL, Z. CULIG, Alois KOZUBÍK and Karel SOUČEK. Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells. \textit{Oncotarget}. Albany: Impact Journals, 2015, vol.~6, No~34, p.~36156-36171. ISSN~1949-2553. Available from: https://dx.doi.org/10.18632/oncotarget.5392.

Detailed Information on Publication Record