CALCR interaction with ANTXR1 drives gastric tumor growth and metastasis via AKT signaling pathway.

This study investigates the role of CALCR, a G-protein-coupled receptor, in gastric cancer (GC) progression and its interaction with ANTXR1. A total of 121 patients with gastric cancer were enrolled from the Department of General Surgery, Anyang Tumor Hospital, Anyang City, Henan Province, China. 218 tumor tissues and corresponding para-carcinoma tissues were collected from 109 patients, while adjacent tissues were retained from the remaining 12 cases. Kaplan-Meier analysis evaluated the prognostic value of m6A-related genes in GC. Immunohistochemistry (IHC) was conducted to evaluate CALCR expression. Quantitative real-time PCR (qRT-PCR), Western blot analysis, CCK-8 assays, flow cytometry and transwell assays were used to assess CALCR's role in cell proliferation, apoptosis, migration, and invasion. Co-immunoprecipitation experiments were performed to explore the interaction between CALCR and ANTXR1. Statistical analyses were conducted using SPSS 25.0 and GraphPad Prism 8.0, with p < 0.05 considered significant. IHC staining revealed that 53.2% (n = 58) of the tumor tissues exhibited high CALCR expression, compared to only 6.6% (n = 8) of the para-carcinoma tissues (p < 0.001). CALCR knockdown in GC cell lines significantly reduced proliferation (p < 0.01), increased apoptosis (p < 0.01), and inhibited migration and invasion (p < 0.001). In a nude mouse model, CALCR knockdown resulted in significantly reduced tumor growth and metastasis (p < 0.05). Co-immunoprecipitation showed that CALCR interacts with ANTXR1, leading to decreased AKT phosphorylation. CALCR is a crucial factor in GC progression, presenting a potential prognostic marker and therapeutic target. Targeting the CALCR-ANTXR1 axis and AKT pathway offers new avenues for GC treatment.