Inducibly decreased MITF levels do not affect proliferation and phenotype switching but reduce differentiation of melanoma cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10375117" target="_blank" >RIV/00216208:11110/18:10375117 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1111/jcmm.13506" target="_blank" >https://doi.org/10.1111/jcmm.13506</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jcmm.13506" target="_blank" >10.1111/jcmm.13506</a>

Result language

angličtina

Original language name

Inducibly decreased MITF levels do not affect proliferation and phenotype switching but reduce differentiation of melanoma cells

Original language description

Melanoma arises from neural crest-derived melanocytes which reside mostly in the skin in an adult organism. Epithelial-mesenchymal transition (EMT) is a tumorigenic programme through which cells acquire mesenchymal, more pro-oncogenic phenotype. The reversible phenotype switching is an event still not completely understood in melanoma. The EMT features and increased invasiveness are associated with lower levels of the pivotal lineage identity maintaining and melanoma-specific transcription factor MITF (microphthalmia-associated transcription factor), whereas increased proliferation is linked to higher MITF levels. However, the precise role of MITF in phenotype switching is still loosely characterized. To exclude the changes occurring upstream of MITF during MITF regulation invivo, we employed a model whereby MITF expression was inducibly regulated by shRNA in melanoma cell lines. We found that the decrease in MITF caused only moderate attenuation of proliferation of the whole cell line population. Proliferation was decreased in five of 15 isolated clones, in three of them profoundly. Reduction in MITF levels alone did not generally produce EMT-like characteristics. The stem cell marker levels also did not change appreciably, only a sharp increase in SOX2 accompanied MITF down-regulation. Oppositely, the downstream differentiation markers and the MITF transcriptional targets melastatin and tyrosinase were profoundly decreased, as well as the downstream target livin. Surprisingly, after the MITF decline, invasiveness was not appreciably affected, independently of proliferation. The results suggest that low levels of MITF may still maintain relatively high proliferation and might reflect, rather than cause, the EMT-like changes occurring in melanoma.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Cellular and Molecular Medicine [online]

ISSN

1582-4934

e-ISSN

—

Volume of the periodical

22

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

2240-2251

UT code for WoS article

000428418200019

EID of the result in the Scopus database

2-s2.0-85041049111