American Association for Cancer Research
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Supplementary Table 4 from The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression

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journal contribution
posted on 2023-04-03, 20:25 authored by Laurie E. Littlepage, Adam S. Adler, Hosein Kouros-Mehr, Guiqing Huang, Jonathan Chou, Sheryl R. Krig, Obi L. Griffith, James E. Korkola, Kun Qu, Devon A. Lawson, Qing Xue, Mark D. Sternlicht, Gerrit J.P. Dijkgraaf, Paul Yaswen, Hope S. Rugo, Colleen A. Sweeney, Colin C. Collins, Joe W. Gray, Howard Y. Chang, Zena Werb

PDF file - 29K, Overlapping adult stem cell signature genes. List of overlapping genes between our dataset (this study) and our adult stem cell signature, which is downregulated in many epithelial cancers relative to normal tissue. Primary MECs overexpressing Znf217 significantly repressed genes of the adult stem cell signature (P=1.89x10-10)



The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.Significance: This study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217. Cancer Discov; 2(7); 638–51. ©2012 AACR.This article is highlighted in the In This Issue feature, p. 569.