CD36 Mediates Palmitate Acid-induced Metastasis Of Gastric Cancer Via AKT/GSK-3?/?-catenin Pathway

Background and Objectives: Gastric cancer(GC)has a clear predilection for metastasis toward omentum primarily composed of adipose tissue,indicating that fatty acids may contribute to this phenomenon.However,their function remains poorly understood in GC.In this study,we aimed to investigate the roles of palmitate acid(PA)and its cellular receptor CD36 in the progression of GC.Methods: Immunohistochemical(IHC)staining was performed to detect the expression level of CD36 in GC tissues and the clinical significance of CD36 was next determined by statistical analysis which was further validated via TCGA and GEO databases.CD36 over-expression and knock-down expression cell models were constructed.Wound healing assay,migration assay,invasion assay and peritoneal implant growth in nude mice were performed to assess the biological effects of PA and CD36.The underlying mechanisms were investigated using western blot,immunofluorescence(IF),quantitative real-time PCR(qRT-PCR)analysis and blocking assay.Results: Here,we demonstrated that PA promoted the metastasis of GC through phosphorylating AKT and then facilitated the nuclear localization of ?-catenin by inactivating GSK-3? via elevating its phosphorylation level,which consequently promoted metastasis of GC both in vitro and in vivo.Furthermore,this tumor-promoting effect induced by PA was manipulated by CD36,a cell surface receptor of fatty acids,of which the expression level in GC tissues positively correlated with the metastasis status of GC patients and negatively correlated with the prognosis of patients using TCGA database,GEO database as well as our own clinical data.Conclusions: Our experiments established CD36 as a key component mediating fatty acids-induced metastasis of GC via AKT/GSK-3?/?-catenin signaling and CD36 might constitute a potential therapeutic target for the clinical intervention of GC.