Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells

Hsi Hsien Hsu, Yueh Min Lin, Chia Yao Shen, Marthandam Asokan Shibu, Shin Yi Li, Sheng Huang Chang, Chien Chung Lin, Ray Jade Chen, Vijaya Padma Viswanadha, Hui Nung Shih, Chih Yang Huang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC). The expression of matrix metalloproteinases (MMPs) has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 αM) promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.

Original languageEnglish
Article numberA1132
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Keywords

  • COX-2
  • EP2 and EP4 receptors
  • Hereditary non-polyposis colon cancer (HNPCC)
  • Prostaglandin E2 (PGE2)
  • β-catenin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Hsu, H. H., Lin, Y. M., Shen, C. Y., Shibu, M. A., Li, S. Y., Chang, S. H., Lin, C. C., Chen, R. J., Viswanadha, V. P., Shih, H. N., & Huang, C. Y. (2017). Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells. International Journal of Molecular Sciences, 18(6), [A1132]. https://doi.org/10.3390/ijms18061132