Details

Autor(en) / Beteiligte

• Cesaro, Elena
• Pastore, Arianna
• Polverino, Alessia
• Manna, Lorenzo
• Divisato, Giuseppina
• Quintavalle, Cristina
• Sanzo, Maddalena Di
• Faniello, Maria Concetta
• Grosso, Michela
• Costanzo, Paola

Titel

ZNF224 is a mediator of TGF-β pro-oncogenic function in melanoma

Ist Teil von

• Human molecular genetics, 2021-11, Vol.30 (22), p.2100-2109

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract The zinc finger protein ZNF224 plays a dual role in cancer, operating as both tumour suppressor and oncogenic factor depending on cellular and molecular partners. In this research we investigated the role of ZNF224 in melanoma, a highly invasive and metastatic cancer, and provided evidence for the involvement of ZNF224 in the TGF-β signalling as a mediator of the TGF-β pro-oncogenic function. Our results showed that ZNF224, whose expression increased in melanoma cell lines after TGF-β stimulation, potentiated the activation induced by TGF-β on its target genes involved in epithelial–mesenchymal transition (EMT). Accordingly, overexpression of ZNF224 enhanced the tumourigenic properties of melanoma cells, promoting cell proliferation and invasiveness, whereas ZNF224 knockdown had the opposite effect. Moreover, ZNF224 positively modulates the expression of TGF-β itself and its type 1 and 2 receptors (TβR1 and TβR2), thus highlighting a possible mechanism by which ZNF224 could enhance the endogenous TGFβ/Smad signalling. Our findings unveil a positive regulatory loop between TGF-β and ZNF224 to promote EMT, consequently increasing the tumour metastatic potential.