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 journalArticle

1 Citation (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 1

Fingerprint

Colorectal Neoplasms
Cyclin D1
Phosphatidylinositols
LY 255283
Lipids
Proto-Oncogene Proteins c-akt
Leukotriene B4
Lipoxygenase
Cell Cycle Checkpoints
Heterografts
Nude Mice
Small Interfering RNA
Up-Regulation
Down-Regulation
Acids
Neoplasms
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells. / Park, Jae In; Jang, Jae Hyun; Kim, Jae-Hong.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1866, No. 3, 01.03.2019, p. 329-336.

Research output: Contribution to journalArticle

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