Phospholipase signalling networks in cancer
Abstract
Phospholipases (PLC, PLD and PLA) are essential mediators of intracellular and intercellular signalling. They can function as phospholipid-hydrolysing enzymes that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid and arachidonic acid. Lipid mediators generated by phospholipases regulate multiple cellular processes that can promote tumorigenesis, including proliferation, migration, invasion and angiogenesis. Although many individual phospholipases have been extensively studied, how phospholipases regulate diverse cancer-associated cellular processes and the interplay between different phospholipases have yet to be fully elucidated. A thorough understanding of the cancer-associated signalling networks of phospholipases is necessary to determine whether these enzymes can be targeted therapeutically.
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Lyso-PLs are mainly synthesized by the enzymatic activity of phospholipases, of which three major classes differing in catalytic activity are known: PLA (consisting of A1 and A2), PLC, and PLD.
“Lyso-PLs are mainly synthesized by the enzymatic activity of phospholipases (26), of which three major classes differing in the catalytic activity are known: PLA (consisting of A1 and A2), PLC, and PLD.”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [26]
PLA1 and PLA2 target the sn-1 and sn-2 positions of phospholipids, respectively, and hydrolyze the ester bond, releasing free fatty acids and Lyso-PLs.
“PLA1 and PLA2 target the sn-1 and sn-2 positions of PLs, respectively, and hydrolyze the ester bond, releasing free fatty acids and Lyso-PLs (26).”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [26]
PLA2 can hydrolyze phospholipids including PC, PS, and PA into arachidonic acid.
“We reasoned that, because of its ability to hydrolyze PLs, including PC, PS, and PA, into AA (26), PLA2 could be a potential target of the anti-ferroptosis activity of sApoE.”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [26]
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References 153 · Cited by 276
- Authors
- Park, J. B., Lee, C. S., Jang, J.-H., Ghim, J., Kim, Y.-J., You, S., Hwang, D., Suh, P.-G., & Ryu, S. H.
- Affiliations
- National Cancer Center (KR)
- Pohang University of Science and Technology (KR)
- Ulsan National Institute of Science and Technology (KR)
- Corresponding author
- Ryu, Sung Ho
- Venue
- Nature Reviews Cancer
- Published
- 2012-10-18
- Volume
- 12
- Issue
- 11
- Pages
- 782-792
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2073361691
- Cited by
- 276
- References
- 153
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 20 · 2023: 41 · 2022: 22 · 2021: 32 · 2020: 12 · 2019: 23 · 2018: 14 · 2017: 20 · 2016: 17 · 2015: 17 · 2014: 12 · 2013: 10 · 2012: 1
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- phospholipase C, phospholipase D, phospholipase A, lipid mediators, diacylglycerol, phosphatidic acid, lysophosphatidic acid, arachidonic acid, carcinogenesis, tumor cell proliferation, tumor cell migration, tumor invasion, angiogenesis
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Neoplasms, Phospholipases, Signal Transduction
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