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Cited by 89Cancer, Lipids, and MetabolismSphingolipid Metabolism and SignalingLipid metabolism and biosynthesis

Secreted phospholipases A2 in cancer: Diverse mechanisms of action

Brglez, Vesna, Lambeau, Gérard, Petan, Toni·2014·Biochimie
DOI 10.1016/j.biochi.2014.09.023
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Abstract

Secreted phospholipases A2 (sPLA2s) hydrolyse cell and lipoprotein phospholipid membranes to release free fatty acids and lysophospholipids, and can also bind to specific proteins. Several sPLA2s have been associated with various cancers, including prostate, colon, gastric, lung and breast cancers, yet, their role is controversial and seems to be dependent on the cancer type, the local microenvironment and the enzyme studied. There is strong evidence that the expression of some sPLA2s, most notably the group IIA, III and X enzymes, is dysregulated in various malignant tissues, where, as described in a number of in vitro and in vivo studies using mouse models and according to correlations between sPLA2 expression and patient survival, a particular enzyme may exert either a pro- or an anti-tumourigenic role. It is becoming clear that there are multiple, context-dependent mechanisms of action of sPLA2s in different cancers. First, the role of sPLA2s in cancer has traditionally been associated with their enzymatic activity and ability to participate in the release of potent biologically active lipid mediators, in particular arachidonic acid-derived eicosanoids, which promote tumourigenesis by stimulating cell proliferation and cell survival, by abrogating apoptosis and by increasing local inflammation and angiogenesis. Second, several biological effects of sPLA2s were found to be independent of sPLA2 enzymatic activity, arguing for a receptor-mediated mechanism of action. Finally, recent studies have implicated sPLA2s in the regulation of basal lipid metabolism, opening a new window to the understanding of the diverse roles of sPLA2s in cancer. In this short review, we highlight the newest findings on the biological roles of sPLA2s in cancer, with emphasis on their diverse mechanisms of action.

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  • Aberrant expression of human group IIA, III and X sPLA2s has been associated with the pathology of colorectal, breast, gastric, oesophageal, ovarian and prostate cancers, providing the potential for phospholipase to be designed as a stimulator in releasing drugs responsively.

    “Secretory phospholipase A2 (sPLA2) is the most studied, aberrant expression of human group IIA (hGIIA), III (hGIII) and X (hGX) sPLA2s has been associated with the pathology of colorectal, breast, gastric, oesophageal, ovarian and prostate cancers, which provide the potential for phospholipase to be designed as a stimulator in releasing drugs responsively.155,156”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [155]

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Authors
Brglez, V., Lambeau, G., & Petan, T.
Affiliations
Jožef Stefan Institute (SI)
Corresponding author
Petan, Toni
ORCID
Venue
Biochimie
Publisher
Elsevier BV
Published
2014-12
Volume
107
Pages
114-123
ISSN
  • 0037-9042 (ISSN-L)
  • 0300-9084
DOI
10.1016/j.biochi.2014.09.023
OpenAlex
W2088049958
Cited by
89
References
146
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 23 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 8
FWCI
2.14
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochimie (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Slovenian Research Agency
  • Slovene Human Resources Development (11012-7/2013-4, 11012-23/2014-8)
  • CNRS
  • Association for International Cancer Research
  • Fondation ARC pour la recherche sur le cancer
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
secretory phospholipase A2, cancer, eicosanoids, arachidonic acid, lysophospholipids, tumor microenvironment, tumor angiogenesis, inflammation, apoptosis, cell proliferation, lipid metabolism, receptor signaling, tumor progression
MeSH terms
Animals, Fatty Acids, Nonesterified, Humans, Isoenzymes, Models, Biological, Neoplasms, Apoptosis, Cell Proliferation, Lipid Metabolism, Phospholipases A2, Secretory

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