ADAMTS7 Enhances Gastric Cancer Growth and Metastasis by Triggering the NF-κB Signaling Pathway

Abstract

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of metalloproteinases plays a vital role in various biological and pathological processes, including tissue remodeling, angiogenesis, and cancer progression. Among the 19 ADAMTS family members, our research focused on ADAMTS7, which exhibited significant overexpression in gastric cancer (GC). This overexpression was strongly correlated with poor clinical outcomes, including reduced overall survival and heightened metastatic potential. To investigate the role of ADAMTS7 in GC, we employed an integrated approach encompassing bioinformatics analysis, Western blotting, immunofluorescence, as well as in vitro and in vivo functional analyses. Our results showed that silencing ADAMTS7 expression significantly inhibited the proliferation, migration, and invasion of GC cells, and furthermore, silencing ADAMTS7 significantly inhibited the growth and metastasis of tumour cells in vivo in nude mice, highlighting its critical role in driving the malignant behaviour of GC cells. Further mechanistic studies identified the NF-κB signaling pathway as a key downstream target of ADAMTS7, with ADAMTS7 silencing resulting in a notable reduction in NF-κB pathway activity. These findings establish ADAMTS7 as a significant contributor to the aggressiveness of GC and a pivotal activator of the NF-κB pathway, a major regulator of inflammation and tumor progression. Consequently, ADAMTS7 emerges as a promising therapeutic target and prognostic biomarker for GC. Our study opens new avenues for the development of targeted therapies aimed at inhibiting ADAMTS7 activity, thereby potentially improving treatment outcomes and survival rates for patients with GC.