Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1
Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribut...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/6/1472 |
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| author | Lara Vecchi Thaise Gonçalves Araújo Fernanda Van Petten de Vasconcelos Azevedo Sara Teixeria Soares Mota Veridiana de Melo Rodrigues Ávila Matheus Alves Ribeiro Luiz Ricardo Goulart |
| author_facet | Lara Vecchi Thaise Gonçalves Araújo Fernanda Van Petten de Vasconcelos Azevedo Sara Teixeria Soares Mota Veridiana de Melo Rodrigues Ávila Matheus Alves Ribeiro Luiz Ricardo Goulart |
| author_sort | Lara Vecchi |
| collection | DOAJ |
| description | Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA<sub>2</sub> are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA<sub>2</sub> leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA<sub>2</sub> and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA<sub>2</sub> in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA<sub>2</sub> and the approaches that could be used in order to resume the anti-PLA<sub>2</sub> function of Annexin A1. |
| first_indexed | 2024-03-10T10:29:45Z |
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| id | doaj.art-e72fb1d4d17c4579a4d925a2e164bb5a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T10:29:45Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e72fb1d4d17c4579a4d925a2e164bb5a2023-11-21T23:48:35ZengMDPI AGCells2073-44092021-06-01106147210.3390/cells10061472Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1Lara Vecchi0Thaise Gonçalves Araújo1Fernanda Van Petten de Vasconcelos Azevedo2Sara Teixeria Soares Mota3Veridiana de Melo Rodrigues Ávila4Matheus Alves Ribeiro5Luiz Ricardo Goulart6Laboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilLaboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilLaboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilLaboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilLaboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilLaboratory of Genetics and Biotechnology, Federal University of Uberlandia, Patos de Minas 387400-128, MG, BrazilLaboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, BrazilPhospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA<sub>2</sub> are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA<sub>2</sub> leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA<sub>2</sub> and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA<sub>2</sub> in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA<sub>2</sub> and the approaches that could be used in order to resume the anti-PLA<sub>2</sub> function of Annexin A1.https://www.mdpi.com/2073-4409/10/6/1472lipid metabolismphospholipase A<sub>2</sub>Annexin A1tumorigenesistumor microenvironmentcancer aggressiveness |
| spellingShingle | Lara Vecchi Thaise Gonçalves Araújo Fernanda Van Petten de Vasconcelos Azevedo Sara Teixeria Soares Mota Veridiana de Melo Rodrigues Ávila Matheus Alves Ribeiro Luiz Ricardo Goulart Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 Cells lipid metabolism phospholipase A<sub>2</sub> Annexin A1 tumorigenesis tumor microenvironment cancer aggressiveness |
| title | Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 |
| title_full | Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 |
| title_fullStr | Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 |
| title_full_unstemmed | Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 |
| title_short | Phospholipase A<sub>2</sub> Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1 |
| title_sort | phospholipase a sub 2 sub drives tumorigenesis and cancer aggressiveness through its interaction with annexin a1 |
| topic | lipid metabolism phospholipase A<sub>2</sub> Annexin A1 tumorigenesis tumor microenvironment cancer aggressiveness |
| url | https://www.mdpi.com/2073-4409/10/6/1472 |
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