Abstract

Oncogenic transcription factor FOXQ1 has been implicated in promotion of multiple transformed phenotypes in carcinoma cells. Recently, we have characterized FOXQ1 as a melanoma tumor suppressor that acts via repression of N-cadherin gene, and invasion and metastasis. Here we report that FOXQ1 induces differentiation in normal and transformed melanocytic cells at least partially via direct transcriptional activation of MITF gene, melanocytic lineage-specific regulator of differentiation. Importantly, we demonstrate that pigmentation induced in cultured melanocytic cells and in mice by activation of cAMP/CREB1 pathway depends in large part on FOXQ1. Moreover, our data reveal that FOXQ1 acts as a critical mediator of BRAFV600E-dependent regulation of MITF levels, thus providing a novel link between two major signal transduction pathways controlling MITF and differentiation in melanocytic cells.

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Acknowledgements

We are grateful to Dr. Smiraglia for critical reading of the manuscript, to the Pathology Resource Network, the Clinical Data Network, and the transgenic shared core facility (funded by NCI P30CA16056) at Roswell Park Cancer Institute. This work has been supported by the following NCI grants: CA190533, CA193981, CA202162, and partially supported by the Program for Basic Research of Russian State Academies of Sciences for 2013−2020.

Author information

Author notes

    • Archis Bagati

    Present address: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Smith Building, SM-0728, 450 Brookline Ave, Boston, MA, 02215, USA

  1. Edited by G Melino

Affiliations

  1. Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

    • Archis Bagati
    • , Anna Bianchi-Smiraglia
    • , Sudha Moparthy
    • , Kateryna Kolesnikova
    • , Emily E. Fink
    • , Masha Kolesnikova
    • , Matthew V. Roll
    • , Peter Jowdy
    • , David W. Wolff
    • , Anthony Polechetti
    • , Dong Hyun Yun
    • , Brittany C. Lipchick
    • , Leslie M. Paul
    • , Brian Wrazen
    • , Kalyana Moparthy
    • , Shaila Mudambi
    • , Gal Shafirstein
    • , Eugene S. Kandel
    • , Gyorgy Paragh
    •  & Mikhail A. Nikiforov
  2. Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russia

    • Galina E. Morozevich
    •  & Albert E. Berman
  3. Institute of Gene Biology, Moscow, Russian Federation

    • Sofia G. Georgieva
  4. Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA

    • Jianmin Wang
    •  & Song Liu
  5. Department of Dermatology, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA

    • Neil F. Box
  6. Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA

    • Gyorgy Paragh

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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Mikhail A. Nikiforov.

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https://doi.org/10.1038/s41418-018-0066-y