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The Hedgehog/GLI signaling pathway activates transcription of Slug (Snail2) in melanoma cells

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10457542" target="_blank" >RIV/00064203:_____/23:10457542 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/23:10457542 RIV/00216208:11110/23:10457542

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LwQi-Y7ZtA" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LwQi-Y7ZtA</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3892/or.2023.8512" target="_blank" >10.3892/or.2023.8512</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    The Hedgehog/GLI signaling pathway activates transcription of Slug (Snail2) in melanoma cells

  • Original language description

    In melanoma and other cancers, invasion, epithelial-to-mesenchymal transition, metastasis and cancer stem cell maintenance are regulated by transcription factors including the Snail family. Slug (Snail2) protein generally supports migration and apoptosis resistance. However, its role in melanoma is not completely understood. The present study investigated the transcriptional regulation of the SLUG gene in melanoma. It demonstrated that SLUG is under the control of the Hedgehog/GLI signaling pathway and is activated predominantly by the transcription factor GLI2. The SLUG gene promoter contains a high number of GLI-binding sites. Slug expression is activated by GLI factors in reporter assays and inhibited by GANT61 (GLI inhibitor) and cyclopamine (SMO inhibitor). SLUG mRNA levels are lowered by GANT61 as assessed by reverse transcription-quantitative PCR. Chromatin immunoprecipitation revealed abundant binding of factors GLI1-3 in the four subregions of the proximal SLUG promoter. Notably, melanoma-associated transcription factor (MITF) is an imperfect activator of the SLUG promoter in reporter assays, and downregulation of MITF had no effect on endogenous Slug protein levels. Immunohistochemical analysis confirmed the above findings and showed MITF-negative regions in metastatic melanoma that were positive for GLI2 and Slug. Taken together, the results demonstrated a previously unrecognized transcriptional activation mechanism of the SLUG gene, which may represent its main regulation of expression in melanoma cells.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30204 - Oncology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Oncology Reports

  • ISSN

    1021-335X

  • e-ISSN

    1791-2431

  • Volume of the periodical

    49

  • Issue of the periodical within the volume

    4

  • Country of publishing house

    GR - GREECE

  • Number of pages

    11

  • Pages from-to

    75

  • UT code for WoS article

    000949302000001

  • EID of the result in the Scopus database

    2-s2.0-85149313717