Fibrinogen Alpha Chain (FGA) Associates With Epithelial-Mesenchymal Transition, Stemness, and the USP-Catenin Complex in Colorectal Cancer.

Abstract

Background: Colorectal cancer (CRC) progression is heavily driven by epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cell (CSC) properties. Elucidating the specific molecular drivers and dynamic indicators underlying these processes is crucial for advancing CRC management.

Methods: The clinical significance and diagnostic value of fibrinogen alpha chain (FGA) were evaluated using TCGA data, immunohistochemistry (IHC), and paired pre- and postoperative serum samples. The biological functions of FGA were assessed in HCT116 cells through Transwell and 3D spheroid formation assays. Immunoprecipitation-mass spectrometry (IP-MS) and protein-protein interaction (PPI) network analyses were utilized to uncover the underlying molecular mechanisms.

Results: FGA mRNA and protein are significantly upregulated in CRC tissues, and preliminary data indicate elevated serum FGA in CRC patients. Clinically, aberrant FGA expression correlates with tumor histological type, lymphatic invasion, and poor survival outcomes. In vitro, FGA overexpression is associated with the downregulation of E-cadherin, upregulation of mesenchymal markers (Vimentin, ZEB1, Snail), and increased cell migration and spheroid formation. Mechanistically, IP-MS identified a potential PPI network wherein FGA associates with ubiquitin-specific proteases (USP7, USP10) and the catenin complex (β-catenin, p120-catenin), suggesting a potential role in mediating pro-stemness signaling.

Conclusion: These findings suggest that FGA may contribute to CRC plasticity by modulating EMT and stem-like properties in vitro. Furthermore, its dynamic postoperative reduction warrants further investigation to determine its utility for non-invasive tumor monitoring.