Although genomic sequencing has provided a better understating of the genetic landmarks in triple-negative breast cancer (TNBC), functional validation of candidate cancer genes (CCG) remains unsolved. In this study, we used a transposon mutagenesis strategy based on a two-step Sleeping Beauty (SB) forward genetic screen to identify and validate new tumor suppressors (TS) in this disease. We generated 120 siRNAs targeting 40 SB-identified candidate breast cancer TS genes and used them to downregulate expression of these genes in four human TNBC cell lines. Among CCG whose SB-mediated genetic mutation resulted in increased cellular proliferation in all cell lines tested, the genes ADNP, AP2B1, TOMM70A and ZNF326 showed tumor suppressor (TS) activity in tumor xenograft studies. Subsequent studies showed that ZNF326 regulated expression of multiple EMT and cancer stem cell (CSC) pathway genes. It also modulated expression of TS genes involved in the regulation of migration and cellular invasion and was a direct transcriptional activator of genes that regulate CSC self-renewal. ZNF326 expression associated with TNBC patient survival, with ZNF326 protein levels showing a marked reduction in TNBC. Our validation of several new tumor suppressor genes in TNBC demonstrate the utility of two-step forward genetic screens in mice, and offer an invaluable tool to identify novel candidate therapeutic pathways and targets.
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
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Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
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Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
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BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
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Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
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Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
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