American Association for Cancer Research
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Table S2 from EMP2 Is a Novel Regulator of Stemness in Breast Cancer Cells

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posted on 2023-04-03, 18:27 authored by Christen Dillard, Meagan Kiyohara, Vei Mah, Sean P. McDermott, Dana Bazzoun, Jessica Tsui, Ann M. Chan, Ghassan Haddad, Matteo Pellegrini, Yu-Ling Chang, Yahya Elshimali, Yanyuan Wu, Jaydutt V. Vadgama, Sara R. Kim, Lee Goodglick, Samuel M. Law, Deven D. Patel, Puneet Dhawan, Neil A. O'Brien, Lynn K. Gordon, Jonathan Braun, Gary Lazar, Max S. Wicha, Madhuri Wadehra

Characteristics of 23 mammary and breast cancer cell lines.

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Charles Drew University

NIH

National Center for Advancing Translational Sciences

NCI

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ARTICLE ABSTRACT

Little is known about the role of epithelial membrane protein-2 (EMP2) in breast cancer development or progression. In this study, we tested the hypothesis that EMP2 may regulate the formation or self-renewal of breast cancer stem cells (BCSC) in the tumor microenvironment. In silico analysis of gene expression data demonstrated a correlation of EMP2 expression with known metastasis-related genes and markers of cancer stem cells (CSC) including aldehyde dehydrogenase (ALDH). In breast cancer cell lines, EMP2 overexpression increased and EMP2 knockdown decreased the proportion of stem-like cells as assessed by the expression of the CSC markers CD44+/CD24−, ALDH activity, or by tumor sphere formation. In vivo, upregulation of EMP2 promoted tumor growth, whereas knockdown reduced the ALDHhigh CSC population as well as retarded tumor growth. Mechanistically, EMP2 functionally regulated the response to hypoxia through the upregulation of HIF-1α, a transcription factor previously shown to regulate the self-renewal of ALDHhigh CSCs. Furthermore, in syngeneic mouse models and primary human tumor xenografts, mAbs directed against EMP2 effectively targeted CSCs, reducing the ALDH+ population and blocking their tumor-initiating capacity when implanted into secondary untreated mice. Collectively, our results show that EMP2 increases the proportion of tumor-initiating cells, providing a rationale for the continued development of EMP2-targeting agents.

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