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@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.
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