ZNF224 enhances the oncogenic function of p21 via p53 and AKT pathways in melanoma

• DOI: 10.1111/febs.70114
• Publication Date: 2025-05-05T09:15:47Z
• Authors: Leandra Sepe; Umberto Candia; Dario Sasso del V...; Elvira Toscano; Marianna Toriello; Gaetano Sodaro; Roberta Rapuano; Simona Romano; Michela Grosso; Giovanni Paolella; Angelo Lupo; Paola Costanzo; Elena Cesaro

Expression of zinc finger protein 224 ( ZNF224 ) is deregulated in various hematological and solid cancers, where its high levels correlate well with faster progression worse prognosis due to activation oncogenic pathways involved promoting cell growth survival, inhibiting apoptosis, sustaining invasion metastasis. In previous works, we identified as one the mediators transforming factor beta (TGF‐β)‐induced pro‐tumoral activities melanoma. present study, thoroughly investigated molecular mechanisms underlying role this kind cancer. We demonstrated that overexpression caused increased reduced drug‐mediated apoptosis by enhancing dysregulated function cyclin‐dependent kinase inhibitor 1 [p21(CIP1/WAF1), also known CDKN1A]. provide strong evidence melanoma lines positively modulated p21(CIP1/WAF1) gene transcription a p53‐dependent manner enhanced AKT‐triggered effects through cytosolic retention, favoring proliferation. Analysis transcriptomic data from human tissue samples confirmed close relationship between cells, at least long p53 functionality maintained. The tumorigenic mechanism involving ZNF224, provides new insights into understanding development progression, breaking ground research for therapeutic tools.