GDF15 promotes gallbladder cancer progression by activating the NF-κB mediated Vascular Endothelial Growth Factor A (VEGFA) expression.

Growth differentiation factor 15 (GDF15) has been found to be elevated in several different types of cancer, thus demonstrating its potential for use as a biomarker. Although its physiological and pathophysiological roles in cancer are increasingly understood, the specific functions and molecular mechanisms of GDF15 in gallbladder cancer remain unclear and require further investigation. Immunohistochemical staining was performed to evaluate the expression of GDF15 in tissue samples from 57 patients with gallbladder cancer. The biological function of GDF15 and the molecular mechanism underlying this were further elucidated through knockdown experiments in NOZ and OCUG-1 gallbladder cancer cell lines. Our results demonstrate that there was a significant correlation be-tween high GDF15 expression and poor survival indicating a poor prognosis in individuals with gallbladder cancer. NanoString analysis results showed that VEGFA, a key angiogenic factor, was significantly upregulated in the GDF15 high-expression group. Moreover, GDF15 knockdown significantly reduced cell motility, as well as migration and invasion. Additionally, GDF15 knockdown in gallbladder cancer cells decreased VEGFA expression via the AKT/NF-κB pathway. Taken together, these results suggest that GDF15 contributes to the aggressive behavior of gallbladder cancer by promoting activation of the AKT/NF-κB pathway. These findings suggest that the GDF15 signaling pathway may represent a promising therapeutic target for gallbladder cancer treatment.