Data from Interaction Between MUC1 and STAT1 Drives IFITM1 Overexpression in Aromatase Inhibitor–Resistant Breast Cancer Cells and Mediates Estrogen-Induced Apoptosis

Abstract

<div>Abstract<p>The human oncoprotein, mucin 1 (MUC1), drives tumorigenesis in breast carcinomas by promoting epithelial-to-mesenchymal transition (EMT), epigenetic reprogramming, and evasion of immune response. MUC1 interacts with STAT1, through JAK/STAT signaling, and stimulates transcription of IFN-stimulated genes, specifically IFN-induced transmembrane protein 1 (IFITM1). Our laboratory has previously shown that IFITM1 overexpression in aromatase inhibitor (AI)-resistant breast cancer cells promotes aggressiveness. Here, we demonstrate that differential regulation of MUC1 in AI-sensitive (MCF-7 and T-47D) compared with AI-resistant (MCF-7:5C) cells is critical in mediating IFITM1 expression. A tumor microarray of 94 estrogen receptor–positive human breast tumors correlated coexpression of MUC1 and IFITM1 with poor recurrence-free survival, poor overall survival, and AI-resistance. In this study, we investigated the effects of MUC1/IFITM1 on cell survival and proliferation. We knocked down MUC1 levels with siRNA and pharmacologic inhibitors, which abrogated IFITM1 mRNA and protein expression and induced cell death in AI-resistant cells. <i>In vivo</i>, estrogen and ruxolitinib significantly reduced tumor size and decreased expression of MUC1, P-STAT1, and IFITM1.</p>Implications:<p>MUC1 and IFITM1 overexpression drives AI resistance and can be targeted with currently available therapies.</p><p><b>Visual Overview:</b> <a href="http://mcr.aacrjournals.org/content/molcanres/17/5/1180/F1.large.jpg" target="_blank">http://mcr.aacrjournals.org/content/molcanres/17/5/1180/F1.large.jpg</a>.</p></div>