Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation
Loss of TET2 promotes activation of PGC-1α/OXPHOS in melanoma, driving metabolic reprogramming that supports tumour progression and resistance to MAPK inhibition in a subset of tumours. Importantly, this phenotype renders TET2-deficient melanomas selectively vulnerable to OXPHOS inhibition, identifying an actionable therapeutic opportunity. These findings establish an epigenetic-metabolic axis as a critical determinant of melanoma aggressiveness and highlight TET2/5-hmC as a potential biomarker and a targetable pathway.
Authors
- Laure Migayron (ORCID: https://orcid.org/0000-0003-2003-1923)
- Gëorge F. Murphy (ORCID: https://orcid.org/0000-0001-9362-5146)
- Elizabeth S. Draper (ORCID: https://orcid.org/0000-0001-9340-8176)
- Rui Fang (ORCID: https://orcid.org/0000-0003-0020-8488)
- Justina Wang
- Tobias Schatton (ORCID: https://orcid.org/0000-0003-1386-680X)
- Shuyun Xu (ORCID: https://orcid.org/0000-0003-2762-4772)
- Grant M. Fischer (ORCID: https://orcid.org/0000-0003-3730-9004)
- Christine G. Lian (ORCID: https://orcid.org/0000-0003-4626-1612)
- Anna Mandinova (ORCID: https://orcid.org/0000-0001-9273-0972)
- Anastasia Iris Karkempetzaki
Institutions
- Broad Institute (US)
- University of North Carolina at Chapel Hill (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Harvard Stem Cell Institute (US)
Publication Details
- Journal
- British Journal of Dermatology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1093/bjd/ljaf378
- Citations
- 1
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.81