Vitamin D/Vitamin D receptor signaling suppresses gastric cancer metastasis through autophagy-related protein 13/Beclin1-mediated autophagy
Year: 2025
Type: article
Abstract: Introduction: Gastric cancer (GC) exhibits a poor prognosis with high metastasis rates. This study investigates Vitamin D receptor’s (VDRs) role in suppressing GC metastasis through autophagy. Objective: To elucidate the molecular mechanism by which VDR suppresses GC invasion and metastasis through autophagy regulation. Methods: VDR expression was assessed in 91 paired GC and adjacent normal tissues using immunohistochemistry. The effects of Vitamin D on GC cell proliferation, cell cycle, migration, and invasion were evaluated using Cell Counting Kit-8, flow cytometry, wound healing, and Transwell assays. The autophagic activity was examined through LysoTracker Red staining, monomeric red fluorescent protein-green fluorescent protein-LC3 fluorescence, and transmission electron microscopy. The roles of VDR, autophagy-related protein 13 (ATG13), and Beclin1 in autophagy regulation were investigated through gene knockdown and silencing. A nude mouse peritoneal metastasis model was used to validate the anti-metastatic effects of the Vitamin D/VDR pathway. Results: VDR expression was significantly downregulated in GC tissues, correlating with lymph node metastasis and poor prognosis (p<0.001). Vitamin D treatment upregulated VDR, ATG13, and Beclin1 expression, enhancing autophagosome and autolysosome formation without altering cell proliferation or apoptosis, likely due to a cytostatic autophagic response. Silencing ATG13 or BECN1 abolished the inhibitory effects of Vitamin D/VDR signaling on cell migration and invasion. VDR knockdown promoted peritoneal metastasis, whereas Vitamin D treatment suppressed it. Conclusion: This study provides novel evidence that Vitamin D/VDR signaling inhibits GC metastasis by influencing ATG13/Beclin1-mediated autophagy, offering potential therapeutic targets for GC management.
Authors: Jinrui Yang, Linyun Tan, Ruolin Shi, Qian Hu, Yinhong Gu, Chao Du
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4413380707