Zhong C, et al. Cancer Sci 2020.
Aberrant activation of ERK (extracellular signal-regulated kinase) signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR (epidermal growth factor receptor) and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models
(Ad-Cre; KrasG12D ; P53f/f ). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of DUSP6 (dual specificity phosphatase 6), a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data demonstrate the tumor-promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target.