Related Experiment Video
Updated: May 9, 2025

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model
Published on: November 13, 2012
ZNF224 enhances the oncogenic function of p21 via p53 and AKT pathways in melanoma
Leandra Sepe1, Umberto Candia1, Dario Sasso Del Verme1
1Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Abstract:
Expression of zinc finger protein 224 (ZNF224) is deregulated in various hematological and solid cancers, where its high protein levels correlate well with faster progression and worse prognosis due to activation of oncogenic pathways involved in promoting cell growth and survival, inhibiting apoptosis, and sustaining invasion and metastasis. In previous works, we identified ZNF224 as one of the mediators of the transforming growth factor beta (TGF-β)-induced pro-tumoral activities in melanoma. In the present study, we thoroughly investigated the molecular mechanisms underlying the oncogenic role of ZNF224 in this kind of cancer. We demonstrated that ZNF224 overexpression caused increased cell growth and reduced drug-mediated apoptosis by enhancing the dysregulated function of cyclin-dependent kinase inhibitor 1 [p21(CIP1/WAF1), also known as CDKN1A]. We provide strong evidence that ZNF224 overexpression in melanoma cell lines positively modulated p21(CIP1/WAF1) gene transcription in a p53-dependent manner and enhanced AKT-triggered p21(CIP1/WAF1) oncogenic effects through its protein cytosolic retention, inhibiting apoptosis and favoring cell proliferation. Analysis of transcriptomic data from human melanoma tissue samples confirmed a close relationship between p21(CIP1/WAF1) and ZNF224 in cells, at least as long as p53 functionality is maintained. The tumorigenic molecular mechanism involving ZNF224, identified in this study, provides new insights into understanding melanoma development and progression, breaking ground in the research for new therapeutic tools.
More Related Videos
06:09Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
08:18Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Intrinsic Apoptotic Pathway
MAPK Signaling Cascades
Abnormal Proliferation
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...