@article{314e97f4c0b14f11b03ed28ee12b7dfc,
title = "EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape",
abstract = "Oncogenic signaling reprograms cancer cell metabolism to augment the production of glycolytic metabolites in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T-cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. EGF signaling, frequently dysregulated in triple-negative breast cancer (TNBC), is also associated with increased glycolysis. Here, we demonstrated in TNBC cells that EGF signaling activates the first step in glycolysis, but impedes the last step, leading to an accumulation of metabolic intermediates in this pathway. Furthermore, we showed that one of these intermediates, fructose 1,6 bisphosphate (F1,6BP), directly binds to and enhances the activity of the EGFR, thereby increasing lactate excretion, which leads to inhibition of local cytotoxic T-cell activity. Notably, combining the glycolysis inhibitor 2-deoxy-D-glucose with the EGFR inhibitor gefitinib effectively suppressed TNBC cell proliferation and tumor growth. Our results illustrate how jointly targeting the EGFR/F1,6BP signaling axis may offer an immediately applicable therapeutic strategy to treat TNBC.",
author = "Lim, {Seung Oe} and Li, {Chia Wei} and Weiya Xia and Lee, {Heng Huan} and Chang, {Shih Shin} and Jia Shen and Hsu, {Jennifer L.} and Daniel Raftery and Danijel Djukovic and Haiwei Gu and Chang, {Wei Chao} and Wang, {Hung Ling} and Chen, {Mong Liang} and Longfei Huo and Chen, {Chung Hsuan} and Yun Wu and Aysegul Sahin and Hanash, {Samir M.} and Hortobagyi, {Gabriel N.} and Hung, {Mien Chie}",
note = "Funding Information: D. Raftery is a CSO and has an ownership interest (including patents) in Matrix-Bio, Inc. No potential conflicts of interest were disclosed by the other authors. This study was funded in part by NIH (CA109311, CA099031, and CCSG CA16672); Susan G. Komen Foundation (SAC110016); Breast Cancer Research Foundation; Patel Memorial Breast Cancer Research Fund; The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund (to M.-C. Hung); Ministry of Science and Technology, International Research-intensive Centers of Excellence in Taiwan (I-RiCE; MOST 104-2911-I-002-302); Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence (MOHW104-TDUB-212-124-002); Center for Biological Pathways; Susan G. Komen for the Cure Postdoctoral Fellowship (PDF12231298 to S.-O. Lim); Basic Science Research Program through the National Research Foundation of Korea funded by the Korea government (MSIP; NRF-2011-357-C00140 to S.-O. Lim); University of Washington and Washington Research Foundation (to D. Raftery). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: {\textcopyright} 2016 American Association for Cancer Research.",
year = "2016",
month = mar,
day = "1",
doi = "10.1158/0008-5472.CAN-15-2478",
language = "English (US)",
volume = "76",
pages = "1284--1296",
journal = "Cancer Research",
issn = "0008-5472",
number = "5",
}