1. Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling
- Author
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Sonia L. Sugg, Weizhou Zhang, Katherine N. Gibson-Corley, Daohong Zhou, Linna Wang, Ryan Kolb, Hank H. Qi, Andrew M. Bellizzi, Yuewan Luo, Qing Xie, Paige Kluz, Qi Liu, Wei Li, Christopher S. Stipp, Ronald J. Weigel, Yinan Zhang, Andy Tao, Myung-Chul Kim, Chen Zhao, Nicholas Borcherding, and Xian Shen
- Subjects
0301 basic medicine ,Isoantigens ,Cancer Research ,Regulator ,Breast Neoplasms ,Receptors, Cell Surface ,Biology ,GPI-Linked Proteins ,Article ,Cell Line ,Pathogenesis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Breast cancer ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,Wnt Signaling Pathway ,Molecular Biology ,beta Catenin ,Cell Proliferation ,Mice, Inbred BALB C ,Cluster of differentiation ,Wnt signaling pathway ,Cell Differentiation ,Epithelial Cells ,medicine.disease ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,MCF-7 Cells ,Cancer research ,Female ,Signal transduction ,Signal Transduction - Abstract
Aiming to identify immune molecules with a novel function in cancer pathogenesis, we found the cluster of differentiation 177 (CD177), a known neutrophil antigen, to be positively correlated with relapse-free (RFS), metastasis-free (MFS) or overall survival (OS) in breast cancer. Additionally, CD177 expression is correlated with good prognosis in several other solid cancers including prostate, cervical, and lung. Focusing on breast cancer, we found that CD177 is expressed in normal breast epithelial cells and is significantly reduced in invasive cancers. Loss of CD177 leads to hyperproliferative mammary epithelium and contributes to breast cancer pathogenesis. Mechanistically, we found that CD177-deficiency is associated with an increase in β-Catenin signaling. Here we identified CD177 as a novel regulator of mammary epithelial proliferation and breast cancer pathogenesis likely via the modulation of Wnt/β-Catenin signaling pathway, a key signaling pathway involved in multiple cancer types.
- Published
- 2020