Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness

Pei Chi Hou, Yo Hua Li, Shih-Chieh Lin, Shao-Chieh Lin, Jenq-Chang Lee, Po-Wen Lin, Jing Ping Liou, Jang-Yang Chang, Ching Chuan Kuo, Yi Min Liu, Hsiao-Fang Sun, Shaw-Jenq Tsai

研究成果: Article

21 引文 (Scopus)

摘要

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 E 2 , which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE 2 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.

原文English
頁(從 - 到)4305-4316
頁數12
期刊Cancer Research
77
發行號16
DOIs
出版狀態Published - 2017 八月 15

指紋

Dual-Specificity Phosphatases
Dual Specificity Phosphatase 2
Colonic Neoplasms
Down-Regulation
Neoplasms
Neoplastic Stem Cells
Prostaglandins E
Histone Deacetylase Inhibitors
Histone Deacetylases
Growth
Hypoxia
Drug Resistance
Colorectal Neoplasms
Signal Transduction
Cell Death
Genome
Pharmacology
Oxygen
Pressure
Food

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

引用此文

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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 E 2 , which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE 2 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.",
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Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness. / Hou, Pei Chi; Li, Yo Hua; Lin, Shih-Chieh; Lin, Shao-Chieh; Lee, Jenq-Chang; Lin, Po-Wen; Liou, Jing Ping; Chang, Jang-Yang; Kuo, Ching Chuan; Liu, Yi Min; Sun, Hsiao-Fang; Tsai, Shaw-Jenq.

於: Cancer Research, 卷 77, 編號 16, 15.08.2017, p. 4305-4316.

研究成果: Article

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AU - Lin, Po-Wen

AU - Liou, Jing Ping

AU - Chang, Jang-Yang

AU - Kuo, Ching Chuan

AU - Liu, Yi Min

AU - Sun, Hsiao-Fang

AU - Tsai, Shaw-Jenq

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