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

作者：Fengyi Mao, Sai Wu, Derek B. Allison, Daheng He, Yifan Kong, Chaohao Li, Zhiguo Li, Yanquan Zhang, Xinyi Wang, Qiongsi Zhang, Chi Wang, Xiaoqi Liu · 发表于：PLoS Biology · 年份：2025 · DOI：10.1371/journal.pbio.3003490 · 被引用次数：4 · 研究领域：Microtubule and mitosis dynamics、Melanoma and MAPK Pathways、PI3K/AKT/mTOR signaling in cancer

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.