Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Abstract

Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum , was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

“…A summary of transgelins about interacted proteins initiating feedback regulations to this signaling and the effects on CRC metastasis is shown in Table 3 . Otherwise, the cartilage oligomeric matrix protein (COMP) interacts with transgelin in EMT to regulate cytoskeletal remodeling and promote malignant progression in CRC ( Zhong et al, 2020 ). Since T-2 phosphorylation is closely related to cell movement, inhibiting T-2 phosphorylation may prevent cell migration and proliferation in CRC ( Leung et al, 2011 ; Sun et al, 2018 ).…”

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1

“…However, the exact pathogenesis of breast cancer is still unclear. In order to provide screening markers and novel therapeutic targets for the prevention and treatment of breast cancer, understanding its pathogenesis at the molecular level is critical (5).…”

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

“…The same study group also showed that TSP-5 expression in breast cancer cells was positively associated with lymph node metastasis and poor survival in the same patients (23). Furthermore, several other investigators have demonstrated that TSP-5 expression is positively related to cell differentiation, T stage, N stage, M stage, and poor outcomes including disease-free and overall survival in colorectal cancer (29)(30)(31). From these reports, our results suggest that TSP-5 plays important roles in malignant behavior and that its expression is a useful predictive marker for survival in patients with BC.…”

“…Unfortunately, there have been no reports on the pathological significance of TSP-5 expression in human BC tissues. However, TSP-5 has been reported to play crucial roles in cell differentiation, tumor growth, invasion, and metastasis in various types of cancers (23,24,(27)(28)(29)(30). For example, TSP-5 expression was significantly associated with Gleason score, T stage, and seminal vesicle invasion in patients with prostate cancer (24).…”