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

14 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

Fingerprint

prostaglandins
Dinoprostone
Colonic Neoplasms
cancer
Cells
Phosphatidylinositols
Catenins
Phosphotransferases
Chemical activation
metastasis
Proteins
Transcription
Cell membranes
Prostaglandin E Receptors
activation
Neoplasm Metastasis
proteins
Matrix Metalloproteinases
cultured cells
Cell Movement

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

Cite this

Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells. / Hsu, Hsi Hsien; Lin, Yueh Min; Shen, Chia Yao; Shibu, Marthandam Asokan; Li, Shin Yi; Chang, Sheng Huang; Lin, Chien Chung; Chen, Ray Jade; Viswanadha, Vijaya Padma; Shih, Hui Nung; Huang, Chih Yang.

In: International Journal of Molecular Sciences, Vol. 18, No. 6, A1132, 01.06.2017.

Research output: Contribution to journalArticle

Hsu, HH, Lin, YM, Shen, CY, Shibu, MA, Li, SY, Chang, SH, Lin, CC, Chen, RJ, Viswanadha, VP, Shih, HN & Huang, CY 2017, 'Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells', International Journal of Molecular Sciences, vol. 18, no. 6, A1132. https://doi.org/10.3390/ijms18061132
Hsu, Hsi Hsien ; Lin, Yueh Min ; Shen, Chia Yao ; Shibu, Marthandam Asokan ; Li, Shin Yi ; Chang, Sheng Huang ; Lin, Chien Chung ; Chen, Ray Jade ; Viswanadha, Vijaya Padma ; Shih, Hui Nung ; Huang, Chih Yang. / Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 6.
@article{634134ac0c6b4da8b7de75568ef5f3e2,
title = "Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells",
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.",
keywords = "COX-2, EP2 and EP4 receptors, Hereditary non-polyposis colon cancer (HNPCC), Prostaglandin E2 (PGE2), β-catenin",
author = "Hsu, {Hsi Hsien} and Lin, {Yueh Min} and Shen, {Chia Yao} and Shibu, {Marthandam Asokan} and Li, {Shin Yi} and Chang, {Sheng Huang} and Lin, {Chien Chung} and Chen, {Ray Jade} and Viswanadha, {Vijaya Padma} and Shih, {Hui Nung} and Huang, {Chih Yang}",
year = "2017",
month = "6",
day = "1",
doi = "10.3390/ijms18061132",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "6",

}

TY - JOUR

T1 - Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells

AU - Hsu, Hsi Hsien

AU - Lin, Yueh Min

AU - Shen, Chia Yao

AU - Shibu, Marthandam Asokan

AU - Li, Shin Yi

AU - Chang, Sheng Huang

AU - Lin, Chien Chung

AU - Chen, Ray Jade

AU - Viswanadha, Vijaya Padma

AU - Shih, Hui Nung

AU - Huang, Chih Yang

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - COX-2

KW - EP2 and EP4 receptors

KW - Hereditary non-polyposis colon cancer (HNPCC)

KW - Prostaglandin E2 (PGE2)

KW - β-catenin

UR - http://www.scopus.com/inward/record.url?scp=85019754319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019754319&partnerID=8YFLogxK

U2 - 10.3390/ijms18061132

DO - 10.3390/ijms18061132

M3 - Article

C2 - 28587064

AN - SCOPUS:85019754319

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - A1132

ER -