FGA inhibits metastases and induces autophagic cell death in gastric cancer via inhibiting ITGA5 to regulate the FAK/ERK pathway

This study aims to investigate the expression levels of fibrinogen ?? chain (FGA) in human gastric cancer (GC) tissues and cell lines, clarify its role in gastric cancer progression, and explore its underlying mechanism. Bioinformatics analysis, Immunoblot, Immunohistochemical (IHC), and quantitative PCR assays were performed to assess the expression of FGA in human gastric cancer tissues and cell lines. CCK-8 and colony formation assays were performed to detect its role in the proliferation of gastric cancer cells. Wound healing, transwell, and Immunofluorescence were performed to detect its effects on gastric cancer cell motility and epithelialmesenchymal transition (EMT) processes. Luciferase and CHIP assays were performed to confirm the transcriptional regulation of FGA on ITGA5. Immunoblot assays and double-label RFP-GFP-LC3 immunofluorescence analysis were conducted to detect its effects on gastric cancer cell autophagy and FAK/ERK pathway, and in vivo tumor growth assays were further performed. We found the low expression of FGA in human gastric cancer tissues and cell lines. FGA suppressed gastric cancer cell proliferation, motility, and EMT process, and stimulated cell autophagy. We further found that FGA suppressed the expression of Integrin-??5 (ITGA5) and inhibited the FAK/ERK pathway, therefore suppressing the progression of gastric cancer. The in vivo assays further confirmed that FGA suppressed tumor growth of gastric cancer cells in the BALB/c nude mice (18???22 g, female, 8-week-old) through suppressing ITGA5-mediated FAK/ERK pathway in mice. We demonstrated the mechanism underlying FGA suppressing gastric cancer progression, and therefore we thought FGA could serve as a tumor suppressor protein in gastric cancer.