The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression
Menée in silico et in vivo, cette étude suggère que l'expression du facteur de transcription ZNF217 est associée à un pronostic défavorable dans le cancer du sein
The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20-30% of primary human breast cancers and correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events to promote increased self-renewal capacity, adult stem cell marker expression, mesenchymal marker expression, invasion and metastasis. By in silico screening, we identified candidate therapeutics that inhibit growth of cancer cells expressing high ZNF217 at low drug concentrations. We demonstrate that the nucleoside analog triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance, and inhibits signaling events (e.g., P-AKT, P-MAPK) in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in breast cancer patients and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Since ZNF217 is amplified in numerous cancers, these results have implications for other cancers.
Cancer Discovery , résumé, 2012