American Association for Cancer Research
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Figure S6 from Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness

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posted on 2023-03-31, 00:41 authored by Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shau-Chieh Lin, Jenq-Chang Lee, Bo-Wen Lin, Jing-Ping Liou, Jang-Yang Chang, Ching-Chuan Kuo, Yi-Min Liu, H. Sunny Sun, Shaw-Jenq Tsai

HDACi abolished hypoxia-induced cancer malignancy

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NSC

NHRI

National Cheng Kung University

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ARTICLE ABSTRACT

Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2–derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2–induced tumor growth and cancer stemness. Genome-wide profile analysis revealed that genes regulated by DUSP2 were similar to those controlled by histone deacetylase. Indeed, treatment with novel histone deacetylase inhibitors abolished hypoxia-induced DUSP2 downregulation, COX-2 overexpression, cancer stemness, tumor growth, and drug resistance. Our findings illuminate mechanisms of cancer stemness and suggest new cancer therapy regimens. Cancer Res; 77(16); 4305–16. ©2017 AACR.