Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells

Jae In Park, Jae Hyun Jang, Jae Hong Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Inflammatory lipid mediators play various roles in colorectal cancer progression through complex pathways. However, the mechanism by which lipoxygenase-derived inflammatory lipid mediators contribute to colorectal cancer progression remains elusive. In this study, we found that BLT2, a cell surface GPCR for leukotriene B4 and 12‑hydroxyeicosatetraenoic acid, is highly upregulated in KRAS mutant LOVO and SW480 colorectal cancer cells and plays critical roles in mediating proliferation through activation of phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) and subsequent upregulation of cyclin D1. Exposure to BLT2 siRNA or LY255283, a specific BLT2 inhibitor, clearly suppressed the proliferation of KRAS mutant colorectal cancer cells and markedly increased cell cycle arrest by downregulating the PI3K/Akt-cyclin D1 cascade. Xenograft tumor formation by LOVO and SW480 cells in athymic mice was also substantially reduced by treatment with the BLT2 inhibitor in vivo. Together, our study demonstrates that BLT2 is necessary for the proliferation of LOVO and SW480 cells and thus may be a potential therapeutic target for the treatment of KRAS mutant colorectal cancer.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1866
Issue number3
DOIs
Publication statusPublished - 2019 Mar

Bibliographical note

Funding Information:
This work was supported by Bio & Medical Technology Development Program Grants ( 2017M3A9D8063317 ) and a Mid-Career Researcher Program Grant ( 2017R1A2B4002203 ) through the National Research Foundation funded by the Ministry of Science, ICT and Future Planning , Republic of Korea. This work was also supported by the BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University).

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Akt
  • BLT2
  • Colorectal cancer
  • KRAS
  • LOVO
  • LTB
  • PI3K
  • Proliferation
  • SW480

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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