2. Academic Validation
  3. The cell cycle regulator PLK1 promotes murine melanoma progression by regulating the transcription factor BACH1

The cell cycle regulator PLK1 promotes murine melanoma progression by regulating the transcription factor BACH1

  • PLoS Biol. 2025 Nov 24;23(11):e3003490. doi: 10.1371/journal.pbio.3003490.
Fengyi Mao 1 2,  Sai Wu 1 2,  Derek B Allison 2 3,  Daheng He 2,  Yifan Kong 1 2,  Chaohao Li 1 2,  Zhiguo Li 1 2,  Yanquan Zhang 1 2,  Xinyi Wang 1 2,  Qiongsi Zhang 1 2,  Chi Wang 2,  Xiaoqi Liu 1 2
Affiliations

Affiliations

  • 1 Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, United States of America.
  • 2 Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America.
  • 3 Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
PMID: 41284701 DOI: 10.1371/journal.pbio.3003490
Abstract

Polo-like kinase 1 (PLK1), a critical cell cycle regulator, is associated with Cancer progression and negatively correlates with patient survival in cutaneous melanoma based on clinical database analysis. In a melanoma mouse model induced by BRafCA mutation and Pten-deficiency, we observed that PLK1 overexpression mediated metabolic reprogramming to markedly accelerate tumor growth, promote metastasis, and shortened mice survival. Mechanistically, PLK1 stabilizes BTB domain and CNC homolog 1 (BACH1), which serves as a crucial transcription factor for genes involved in Cancer Metabolism and Metastasis. Moreover, the PLK1/BACH1 axis confers resistance to Vemurafenib, a BRAFV600E inhibitor, in melanoma. In light of this finding, we attempted an innovative pharmacological combination targeting both BRAFV600E and PLK1, identifying a synergistic efficiency to this approach to suppress tumor growth. Overall, we have discovered a novel function of PLK1 that is independent of the cell cycle, which could pave new ways for melanoma therapies.

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