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

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

研究成果: 雜誌貢獻文章

27 引文 斯高帕斯(Scopus)


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.
頁(從 - 到)4305-4316
期刊Cancer Research
出版狀態已發佈 - 八月 15 2017


ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Hou, P. C., Li, Y. H., Lin, S. C., Lin, S. C., Lee, J. C., Lin, B. W., Liou, J. P., Chang, J. Y., Kuo, C. C., Liu, Y. M., Sun, H. S., & Tsai, S. J. (2017). Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness. Cancer Research, 77(16), 4305-4316. https://doi.org/10.1158/0008-5472.CAN-16-2990