Identification of AXL as a novel positive regulator of lipid raft in gastric cancer

• Published in: Cellular signalling 2025-03, Vol.127, p.111573, Article 111573
• Main Authors: Yang, Zhi, Ren, Chuanfu, He, Ziyun, Luo, Banxin, Chen, Xin, Xu, En, Guan, Wenxian, Xia, Xuefeng
• Format: Article
• Language: English
• Subjects: AXL; Caveolae; Gastric cancer; Lipid raft; WGCNA
• ISSN: 0898-6568; 1873-3913; 1873-3913
• DOI: 10.1016/j.cellsig.2024.111573

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. [Display omitted] •High lipid raft levels predict poor prognosis in gastric cancer patients.•Modulating lipid raft levels alters gastric cancer cell proliferation and invasion.•AXL interacts with Caveolin-1 to promote lipid raft formation and AKT signaling.•High AXL expression correlates with poor survival in gastric cancer patients.•AXL knockdown inhibits tumor growth and metastasis in vivo.