American Association for Cancer Research
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Supplementary Tables from HER2 Overexpression Triggers an IL1α Proinflammatory Circuit to Drive Tumorigenesis and Promote Chemotherapy Resistance

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posted on 2023-03-31, 02:28 authored by Shou Liu, Ji Shin Lee, Chunfa Jie, Min Ho Park, Yoichiro Iwakura, Yogin Patel, Mithil Soni, David Reisman, Hexin Chen

Supplementary Tables - Supplementary Tables S1, S3 and S4. S1 shows frequency of CSCs after transplantation of the indicated cells. S3 shows multivariate Cox regression data. S4 Positive correlation between IL-1α and HER2 or IL6 expression in breast cancer tissues.

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ARTICLE ABSTRACT

Systemic inflammation in breast cancer correlates with poor prognosis, but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation, and expansion of the mammary stem/progenitor and cancer stem–like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feedforward activation loop of IL1α and IL6 that stimulated NFκB and STAT3 pathways for generation and maintenance of breast CSC. In mice, Il1a genetic deficiency delayed MMTV-Her2–induced tumorigenesis and reduced inflammatory cytokine expression as well as CSC in primary tumors. In clinical specimens of human breast tumor tissues, tissue microarray analysis revealed a strong positive correlation between IL1α/IL6 expression and CSC-positive phenotype. Pharmacologic blockade of IL1α signaling reduced the CSC population and improved chemotherapeutic efficacy. Our findings suggest new therapeutic or prevention strategies for HER2-positive breast cancers.Significance: IL1α signaling driven by HER2 promotes chronic inflammation needed to support cancer stem-like cell maintenance in HER2-positive breast cancers. Cancer Res; 78(8); 2040–51. ©2018 AACR.