O-GlcNAcylation of ITGA5 facilitates the occurrence and development of colorectal cancer

Background/objective: Integrin alpha 5 (ITGA5) as one member of integrins family, plays an important role in promoting cancer cell metastasis and invasion through inducing the communications among different cells or cells with extracellular matrix (ECM). However, the mechanisms underlying ITGA5 in colorectal cancer (CRC) progression need to be explored, especially for its O-GlcNAcylation. To this end, the current study was performed to explore the effects of O-GlcNAcylation on ITGA5 expression, as well as to probe the effects of ITGA5 O-GlcNAcylation on CRC progression. Methods: The expression profiles of ITGA5, OGT and O-GlcNAc in CRC tissues and cells were detected by immunohistochemistry (IHC), RT-PCR and western blotting. CCK-8, flow cytometry and xenotransplantation assays were used to assess cell growth, apoptosis and tumorigenesis. Immunoprecipitation (IP), in vitro O-GlcNAcylation of ITGA5 and enzymatic labelling of O-GlcNAc assays were used to detect the O-GlcNAcylation of ITGA5 protein. Results: The expression of ITGA5, OGT and O-GlcNAc were all elevated in CRC tissues and cells compared with the normal tissues and cells. Up-regulation of ITGA5 in CRC RKO cells enhanced cell growth and tumorigenesis while decreased cell apoptosis, while down-regulation of ITGA5 in CRC SW620 cells decreased cell growth and tumorigenesis and induced cell apoptosis. Besides, PUGNAc, GlcN or PUGNAc + GlcNAc treatment increased ITGA5 protein expression in RKO and SW620 cells, as well as increased its protein stability via enhancing its O-GlcNAcylation. Conclusion Collectively, the present study makes clear that ITGA5 overexpression accelerates the progression of CRC, which is closely associated to its enhanced O-GlcNAcylation.