The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer.

Saliakoura, Maria; Reynoso-Moreno, Inés; Pozzato, Chiara; Rossi Sebastiano, Matteo; Galié, Mirco; Gertsch, Jürg; Konstantinidou, Georgia (2020). The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer. Oncogene, 39(14), pp. 2948-2960. Springer Nature 10.1038/s41388-020-1196-5

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Enhanced prostaglandin production promotes the development and progression of cancer. Prostaglandins are generated from arachidonic acid (AA) by the action of cyclooxygenase (COX) isoenzymes. However, how cancer cells are able to maintain an elevated supply of AA for prostaglandin production remains unclear. Here, by using lung cancer cell lines and clinically relevant KrasG12D-driven mouse models, we show that the long-chain acyl-CoA synthetase (ACSL3) channels AA into phosphatidylinositols to provide the lysophosphatidylinositol-acyltransferase 1 (LPIAT1) with a pool of AA to sustain high prostaglandin synthesis. LPIAT1 knockdown suppresses proliferation and anchorage-independent growth of lung cancer cell lines, and hinders in vivo tumorigenesis. In primary human lung tumors, the expression of LPIAT1 is elevated compared with healthy tissue, and predicts poor patient survival. This study uncovers the ACSL3-LPIAT1 axis as a requirement for the sustained prostaglandin synthesis in lung cancer with potential therapeutic value.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Saliakoura, Maria; Reynoso, Ines del Carmen; Pozzato, Chiara; Rossi Sebastiano, Matteo; Gertsch, Jürg and Konstantinidou, Georgia

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1476-5594

Publisher:

Springer Nature

Language:

English

Submitter:

Celine Joray

Date Deposited:

18 Feb 2020 15:13

Last Modified:

12 Mar 2021 04:53

Publisher DOI:

10.1038/s41388-020-1196-5

PubMed ID:

32034305

BORIS DOI:

10.7892/boris.140211

URI:

https://boris.unibe.ch/id/eprint/140211

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