Skip to content
DraconiticResearch
Search Sources API
220,618 studies31 sourcesUpdated 15 min ago
Peer-reviewedCC BY 4.0Molecular Oncology

MITF maintains genome stability in nonmelanocyte lineages

  • Drifa H. Gudmundsdottir1,2,3
  • Adrián López García de Lomana2
  • Thejus B. Venkatesh1,2
  • Kritika Kirty1,2
  • Snaevar Sigurdsson2
  • Linda Vidarsdottir1,2
  • Ramile Dilshat2
  • Erla Sveinbjornsdottir4
  • Snaedis Ragnarsdottir1,2
  • Daniel H Magnusson1,2
  • Maria R. Bustos1,2
  • Eirikur Steingrimsson1,2
2 more authors
  • Thorkell Gudjonsson1,2,5
  • Stefan Sigurdsson1,2
5 affiliations
  1. 1Cancer Research Laboratory, Faculty of Medicine, University of Iceland Reykjavik Iceland
  2. 2Biomedical Center, University of Iceland Reykjavik Iceland
  3. 3Department of Molecular Oncology University Hospital of Iceland Reykjavik Iceland
  4. 4Department of Genetics and Molecular Medicine University Hospital of Iceland Reykjavik Iceland
  5. 5Biotech Research & Innovation Center, University of Copenhagen Denmark
Read full textDOICite

Abstract

Microphthalmia‐associated transcription factor (MITF) is crucial for development and survival of melanocytes and serves as a lineage‐specific oncogene that is amplified in 10–20% of melanomas. The role of MITF in pathways maintaining genome integrity, such as DNA replication, DNA repair, and mitosis has been extensively studied in melanocytes. In addition to its pro‐survival role in melanoma, recent studies have shown that MITF expression has important implications for cancer progression and treatment in other cancer types. Nevertheless, studies on the role of MITF in other tissues are scarce. Here, we show that depletion of MITF causes genome instability in nonmelanocytic cell lineages, which results in activation of P53, cell cycle arrest, and apoptosis. Moreover, we show that P53 activation in MITF‐depleted cells is dependent on LATS2, a kinase with an established role in the Hippo pathway. Finally, we show that LATS2 mediated upregulation of P53 is ATR‐dependent. Collectively, this study highlights the role of MITF as a genome maintenance factor beyond the melanocyte lineage, which might contribute to the tumor suppressive function of MITF.

Related

  1. THE MULTIFUNCTIONAL PROTEIN E4F1 REGULATES MELANOCYTIC FUNCTIONS IN MICE THROUGH PROTEIN TRANSLATION AND MITF EXPRESSION
    M. Rousseau, M. Houdeville, L. Henry +18
    bioRxivPreprintAll rights reservedFull textPhysiologybioRxiv
  2. LncRNA Gas5 directs SUV39H2 to establish heterochromatin and maintain genome stability
    Juntao Liu, Jiani Yang, Wen Ye +6
    Protein & CellPeer-reviewedCC BY 4.0Full textOncologyPMC
  3. Fructus Sophorae Extract Generated Using the Natural Deep Eutectic Solvent ChCl Urea Activates Wnt/β Catenin and cAMP/MITF Signaling to Stimulate Hair Growth and Pigmentation
    Gary Ka-Wing Yuen, Yinzhi Li, Tina Ting-Xia Dong +1
    International journal of molecular sciencesPeer-reviewedCC BYFull textGeneral medicineEurope PMCCrossref
  4. CDKN3 in cancer: context-dependent cell-cycle control and implications for genome stability and therapy
    Yi Li, Long Cheng, Xiaowei Zhang +2
    Frontiers in OncologyPeer-reviewedCC BY 4.0Full textOncologyCrossrefDOAJ
  5. TNIK maintains a MYC-driven partial EMT state that supports proliferation and evasion of senescence in lung squamous cell carcinoma.
    P. Torres-Ayuso, M. Hamidi, K. O. Omolo +3
    bioRxivPreprintAll rights reservedFull textOncologybioRxiv

Cite

BibTeXRIS
BibTeX
@article{gudmundsdottir2026mitf,
  title = {{MITF maintains genome stability in nonmelanocyte lineages}},
  author = {Drifa H. Gudmundsdottir and Adrián López García de Lomana and Thejus B. Venkatesh and Kritika Kirty and Snaevar Sigurdsson and Linda Vidarsdottir and Ramile Dilshat and Erla Sveinbjornsdottir and Snaedis Ragnarsdottir and Daniel H Magnusson and Maria R. Bustos and Eirikur Steingrimsson and Thorkell Gudjonsson and Stefan Sigurdsson},
  journal = {Molecular Oncology},
  year = {2026},
  month = jun,
  doi = {10.1002/1878-0261.70273},
  url = {https://doi.org/10.1002/1878-0261.70273},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - MITF maintains genome stability in nonmelanocyte lineages
AU  - Drifa H. Gudmundsdottir
AU  - Adrián López García de Lomana
AU  - Thejus B. Venkatesh
AU  - Kritika Kirty
AU  - Snaevar Sigurdsson
AU  - Linda Vidarsdottir
AU  - Ramile Dilshat
AU  - Erla Sveinbjornsdottir
AU  - Snaedis Ragnarsdottir
AU  - Daniel H Magnusson
AU  - Maria R. Bustos
AU  - Eirikur Steingrimsson
AU  - Thorkell Gudjonsson
AU  - Stefan Sigurdsson
PY  - 2026
DA  - 2026/06/10
JO  - Molecular Oncology
DO  - 10.1002/1878-0261.70273
UR  - https://doi.org/10.1002/1878-0261.70273
AB  - Microphthalmia‐associated transcription factor (MITF) is crucial for development and survival of melanocytes and serves as a lineage‐specific oncogene that is amplified in 10–20% of melanomas. The role of MITF in pathways maintaining genome integrity, such as DNA replication, DNA repair, and mitosis has been extensively studied in melanocytes. In addition to its pro‐survival role in melanoma, recent studies have shown that MITF expression has important implications for cancer progression and treatment in other cancer types. Nevertheless, studies on the role of MITF in other tissues are scarce. Here, we show that depletion of MITF causes genome instability in nonmelanocytic cell lineages, which results in activation of P53, cell cycle arrest, and apoptosis. Moreover, we show that P53 activation in MITF‐depleted cells is dependent on LATS2, a kinase with an established role in the Hippo pathway. Finally, we show that LATS2 mediated upregulation of P53 is ATR‐dependent. Collectively, this study highlights the role of MITF as a genome maintenance factor beyond the melanocyte lineage, which might contribute to the tumor suppressive function of MITF.
SN  - 1574-7891
SN  - 1878-0261
ER  -