Zhi Yang , Chuanfu Ren , Ziyun He , Banxin Luo , Xin Chen , En Xu , Wenxian Guan , Xuefeng Xia
{"title":"Identification of AXL as a novel positive regulator of lipid raft in gastric cancer","authors":"Zhi Yang , Chuanfu Ren , Ziyun He , Banxin Luo , Xin Chen , En Xu , Wenxian Guan , Xuefeng Xia","doi":"10.1016/j.cellsig.2024.111573","DOIUrl":null,"url":null,"abstract":"<div><div>Lipid rafts are highly heterogeneous and dynamic microdomains involved in molecule trafficking and signaling transduction. This study investigates the role of lipid rafts in gastric cancer and their key regulators. Analyzing FFPE samples from 111 gastric cancer patients, we found that high lipid raft levels predict poor prognosis. Modulating these levels in gastric cancer cell lines significantly impacted cell proliferation, migration, and invasion. Weighted Gene Co-expression Network Analysis identified AXL as a hub gene associated with lipid rafts. AXL knockdown experiments revealed its interaction with Caveolin-1, a caveolae lipid raft protein, which regulates lipid raft levels and promotes AKT and ERK signaling, enhancing cancer development and metastasis. In vivo tumorigenesis assays and survival analyses further supported these findings. This study underscores the significance of lipid rafts in gastric cancer and identifies AXL as a novel regulator, offering new insights into the molecular mechanisms of cancer progression and suggesting potential therapeutic targets.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111573"},"PeriodicalIF":4.4000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular signalling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0898656824005497","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Lipid rafts are highly heterogeneous and dynamic microdomains involved in molecule trafficking and signaling transduction. This study investigates the role of lipid rafts in gastric cancer and their key regulators. Analyzing FFPE samples from 111 gastric cancer patients, we found that high lipid raft levels predict poor prognosis. Modulating these levels in gastric cancer cell lines significantly impacted cell proliferation, migration, and invasion. Weighted Gene Co-expression Network Analysis identified AXL as a hub gene associated with lipid rafts. AXL knockdown experiments revealed its interaction with Caveolin-1, a caveolae lipid raft protein, which regulates lipid raft levels and promotes AKT and ERK signaling, enhancing cancer development and metastasis. In vivo tumorigenesis assays and survival analyses further supported these findings. This study underscores the significance of lipid rafts in gastric cancer and identifies AXL as a novel regulator, offering new insights into the molecular mechanisms of cancer progression and suggesting potential therapeutic targets.
期刊介绍：
Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo.
Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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