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This review summarizes dual mechanisms: promotion through EMT induction, GPX4-mediated resistance to ferroptosis, and VEGF-dependent angiogenesis, while suppression occurs via Wnt/β-catenin inhibition in BRCA1-mutated breast cancers or by enhanced apoptosis. It also discusses Lp-PLA2 interactions with Notch and HIF1α pathways and highlights microenvironment-guided targeting strategies, supporting its value as a prognostic biomarker and therapeutic target, informing future innovative approaches.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/lp-pla2-in-the-cancer-landscape-from-molecular-mechanisms-to-therapeutic-potential-review/370903/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/lp-pla2-in-the-cancer-landscape-from-molecular-mechanisms-to-therapeutic-potential-review/370903.png","ImageObject",300,407,{"name":42,"@type":43},"Franzy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-26","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is Lp-PLA2 and why is it important in cancer research?","Question",{"text":63,"@type":64},"Lp-PLA2 is lipoprotein-associated phospholipase A2, originally studied for proinflammatory roles in cardiovascular diseases. Recent evidence links it to tumorigenesis with context-dependent pro- and anti-tumor functions.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does Lp-PLA2 promote cancer progression?",{"text":68,"@type":64},"As a tumor promoter, Lp-PLA2 promotes cancer progression via EMT induction, GPX4-mediated resistance to ferroptosis, and VEGF-dependent angiogenesis.",{"name":70,"@type":61,"acceptedAnswer":71},"How can Lp-PLA2 act as a tumor suppressor?",{"text":72,"@type":64},"As a tumor suppressor, Lp-PLA2 inhibits tumor growth by suppressing the Wnt/β-catenin pathway in BRCA1-mutated cancers or by promoting apoptosis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},370903,1790263197,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","INTERNATIONAL JOURNAL OF ONCOLOGY 67: 87, 2025  \nLp‑PLA2 in the cancer landscape: From molecular mechanisms to therapeutic potential (Review)  \nXIAORONG YANG 1* , YONGBO TU2* , NA LIANG3 , LINGLI LI4 ,  \nJIAN ZHANG5 , JINGYU XU6 and CHUNMING LI3  \n1Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China; 2Department of Radiology, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China; 3Department of Pathology,  \n4  \nThe First Clinical Medical College of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China; Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China; 5Department of Cardiac Macrovascular Surgery,  \n6  \nAffiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China; The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China  \nReceived June 18, 2025; Accepted July 30, 2025  \nDOI: 10.3892/ijo.2025.5793  \nAbstract . Lipoprotein‑associated phospholipa se A2 (Lp‑PLA2), an important member of the phospholipase A2 superfamily, was originally investigated for its proinflammatory role in cardiovascular diseases. Recent studies have revealed its significant role in tumorigenesis: It can act as either a tumor promoter or a tumor suppressor depending on the context. The present review systematically outlined the dual mechanisms by which Lp‑PLA2 contributes to cancer pathogenesis. Asa tumor promoter, it promotes cancer progression via the induction of epithelial‑mesenchymal transition, glutathione peroxidase 4‑mediated resistance to ferroptosis, and vascular endothelial growth factor‑dependent angiogenesis; conversely, as a tumor suppressor, it inhibits tumor growth by suppressing the Wnt/β‑catenin pathway in breast cancer gene 1‑mutated cancers or by promoting apoptosis. Mechanistic investigations clarify the interactions between Lp‑PLA2 and critical onco‑ genic pathways, such as the Notch and HIF1α pathways, while emphasizing the functional dichotomy that is influenced by  \nCorrespondence to: Professor Chunming Li, Department of Pathology, The First Clinical Medical College of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, Guizhou 563003, P.R. China  \nE‑mail: [licm@zmu.edu.cn](licm@zmu.edu.cn)  \nProfessor Jingyu Xu, The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, 6 Xuefu West Road, Xinpu, Zunyi, Guizhou 563006, P.R. China  \nE‑mail: [xujingyu_gzzy@126.com](xujingyu_gzzy@126.com)  \n*Contributed equally  \nAbbreviations: AA, arachidonic acid; ALDH, aldehyde dehydrogenase; BRCA1, breast cancer gene 1; CPT1A, carnitinepalmitoyltransferase 1a; CSCs, cancer stem cells; DLBCL, large b‑cell lymphoma; EMT, epithelial‑mesenchymal transition; FASN, fatty  \nthe microenvironment. Current evidence supports the devel‑ opment of microenvironment‑guided targeting strategies and the potential value of Lp‑PLA2 as a prognostic biomarker and therapeutic target. These findings contribute to a theoretical framework for comprehending the context‑dependent roles of Lp‑PLA2 and may guide the development of innovative therapeutic approaches.  \nContents  \n1. Introduction  \n2. The role of Lp‑PLA2 in tumorigenesis mechanisms  \n3. The dual role of Lp‑PLA2 in tumor development  \n4. Lp‑PLA2 and the TME  \n5. Lp‑PLA2 as a tumor biomarker  \n6. Therapeutic strategies targeting Lp‑PLA2 in tumors  \n7. Conclusions and future perspectives  \nacid synthase; GPX4, glutathione peroxidase 4; HCC, hepatocellular carcinoma; 12‑HETE‑PPARγ, 12‑Hydroxyeicosatetraenoic Acid‑ Peroxisome Proliferator‑Activated Receptor Gamma; LDL, low‑density lipoprotein; Lp‑PLA2, lipoprotein‑associated phos‑ pholipase a2; LPC, lysophosphatidylcholine; ox‑FFA, oxidized free fatty acids; PAF, platelet‑activating factor; PAF‑AH, platelet‑ activating factor acetylhyd","cbCaiaojvUuBStke","https://ap.wps.com/l/cbCaiaojvUuBStke","pdf",3194118,17,"English","# Introduction\n# The role of Lp-PLA2 in tumorigenesis mechanisms\n# The dual role of Lp-PLA2 in tumor development\n# Lp-PLA2 and the TME\n# Lp-PLA2 as a tumor biomarker\n# Therapeutic strategies targeting Lp-PLA2 in tumors\n# Conclusions and future perspectives","[{\"question\":\"What is Lp-PLA2 and why is it important in cancer research?\",\"answer\":\"Lp-PLA2 is lipoprotein-associated phospholipase A2, originally studied for proinflammatory roles in cardiovascular diseases. Recent evidence links it to tumorigenesis with context-dependent pro- and anti-tumor functions.\"},{\"question\":\"How does Lp-PLA2 promote cancer progression?\",\"answer\":\"As a tumor promoter, Lp-PLA2 promotes cancer progression via EMT induction, GPX4-mediated resistance to ferroptosis, and VEGF-dependent angiogenesis.\"},{\"question\":\"How can Lp-PLA2 act as a tumor suppressor?\",\"answer\":\"As a tumor suppressor, Lp-PLA2 inhibits tumor growth by suppressing the Wnt/β-catenin pathway in BRCA1-mutated cancers or by promoting apoptosis.\"}]","Lp-PLA2 in the cancer landscape - From molecular mechanisms to therapeutic potential - Review | PDF",1790190797,43]