Phospholipase A₂ Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Cells
• Subjects: lipid metabolism; phospholipase A₂; Annexin A1; tumorigenesis; tumor microenvironment; cancer aggressiveness
• Online Access: https://www.mdpi.com/2073-4409/10/6/1472

Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A₂ (PLA₂) 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 PLA₂ 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 PLA₂ 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 PLA₂ and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA₂ 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 PLA₂ and the approaches that could be used in order to resume the anti-PLA₂ function of Annexin A1.