<p>A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) protease family involves a critical member ADAMTS6, which is implicated in the pathogenesis of various cancers. This study explores the function of ADAMTS6 in tumor growth and angiogenesis in gastric carcinoma (GC). Using the TCGA-STAD dataset, key genes closely associated with GC prognosis were screened, and their correlation with the angiogenesis pathway was evaluated. In vitro, a GC cell model with ADAMTS6 knockdown was established, and cell proliferation, migration, invasion, and apoptosis were systematically assessed. The regulatory effect of ADAMTS6 on the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) was determined via tube formation assay. In vivo, a GC xenograft mouse model was established to monitor tumor growth, and the effects of ADAMTS6 knockdown on tumor proliferation, apoptosis, and angiogenesis were comprehensively evaluated using immunohistochemistry, TUNEL staining, immunofluorescence, and Western blot analysis. ADAMTS6 was highly expressed in GC tissues and cell lines, and its expression was positively correlated with poor prognosis and tumor angiogenesis. Silencing ADAMTS6 significantly inhibited GC cell proliferation, migration, and invasion, while inducing apoptosis and attenuating the pro-angiogenic effect on HUVECs in vitro. Consistently, in vivo experiments confirmed that ADAMTS6 knockdown markedly suppressed tumor growth, as evidenced by reduced tumor volume and weight. Moreover, the expression of angiogenesis-related markers was downregulated following ADAMTS6 silencing. ADAMTS6 facilitates tumor growth and angiogenesis in GC and might act as a valuable biomarker for prognosis and a candidate target for anti-angiogenic therapeutic approaches.</p> Graphical Abstract <p>Mechanism diagram of ADAMTS6 promoting angiogenesis and tumor growth in gastric carcinoma.</p> <p></p>