ABSTRACT: Background: Gastric cancer (GC) is a serious malignant disease of digestive system over the world. Angiopoietin-like protein 4 (ANGPTL4) was a secreted glycoprotein, which involved in multiple pathophysiological process, such as metabolic reprogramming, angiogenesis, proliferation and metastasis. Nevertheless, the expression, function, and prognostic significance of ANGPTL4 in GC are still contradictory. Methods: Bioinformatic analysis to confirm the expression and prognosis of ANGPTLs in GC. IF staining was used to detect ANGPTL4 protein in GC samples. The molecular biological effect of ANGPTL4 was confirmed by EdU, MTT, FCS, wound healing, transwell, tube formation chorioallantoic membrane model, and nude mice model assay in GC cell lines. RNA-seq was used to confirm the potential downstream mechanism of ANGPTL4, which verified by PCR, WB, IF, co-IP and molecular docking. Results: ANGPTL4, as an important ANGPTLs, was significantly correlated with poor diagnosis in GC patients. The proliferation, migration, invasion, apoptosis escaping, angiogenesis ability was enhanced by ANGPTL4 in SNU5 and MKN7, but repressed in AGS. LGALS7 could be upregulated in AGS transfected with ANGPTL4 OE, which was one of the key factors that cause ANGPTL4 to produce an anticancer phenotype. Conclusion: LGALS7 was a key factor for the contradictory effect of ANGPTL4 on activating hedgehog pathway to driving GC progression, including proliferation, migration, apoptosis escaping, angiogenesis and lymphangiogenesis.
