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
  • 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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