Upregulation of C-C chemokine receptor type 7 expression by membrane-associated prostaglandin E synthase-1/prostaglandin E2 requires glycogen synthase kinase 3β-mediated signal transduction in colon cancer cells

Yu,Shuyi; Hou,Qian; Sun,Huiping; Liu,Jianping; Li,Jianzhe

doi:10.3892/mmr.2015.4290

Upregulation of C-C chemokine receptor type 7 expression by membrane-associated prostaglandin E synthase-1/prostaglandin E2 requires glycogen synthase kinase 3β-mediated signal transduction in colon cancer cells

Authors:
- Shuyi Yu
- Qian Hou
- Huiping Sun
- Jianping Liu
- Jianzhe Li
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Affiliations: Advanced Research Center, Central South University, Changsha, Hunan 410008, P.R. China, Department of Nutrition, Xaingya Hospital, Central South University, Changsha, Hunan 410002, P.R. China, Department of Anesthesia, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410006, P.R. China, Department of Pharmacy, Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China
Published online on: September 3, 2015 https://doi.org/10.3892/mmr.2015.4290
Pages: 7169-7175

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Abstract

C-C chemokine receptor type 7 (CCR7) is involved in the development and progressions of chronic inflammatory diseases and cancer; therefore, signaling pathways that regulate CCR7 expression may represent novel molecular therapeutic targets. Previous studies by our group revealed that CCR7 is important in colon cancer progression and a is linked with cyclooxygenase (COX)‑2‑derived prostaglandin (PG)E2. Induction of COX‑2 and membrane‑associated PGE synthase 1 (mPGES‑1), which are overexpressed in numerous cancer types, cooperatively enhance PGE2 expression, which contributes to carcinogenesis and cancer progression. The present study investigated whether CCR7 expression is associated with the levels of mPGES‑1-derived PGE2. The results showed that mPGES‑1‑dependent release of PGE2 was markedly induced in colon cancer cells after transient transfection with mPGES‑1 overexpression vector, accompanied by elevated CCR7 expression. PGE2 levels and CCR7 expression were markedly attenuated in colon cancer cells in which mPGES‑1 was blocked, which identified mPGES‑1 as a potential therapeutic target for the regulation of CCR7 expression. Finally, overexpression of CCR7 was partly mediated through the AKT/glycogen synthase kinase 3β signaling pathway dependent on the binding of mPGES‑1-derived PGE2 to the prostaglandin EP4 receptor. Thus, in addition to inhibitors of mPGES‑1 expression, EP4 antagonists and AKT/GSK-3β inhibitors may emerge as potential therapeutics to reduce CCR7 expression in colon cancer.

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