Nucleotide Sugar Transporter SLC35A2 Is Involved In Promoting Metastatic Potential Of Hepatocellular Carcinoma

Abstract Purpose Recently, aberrant glycosylation has been recognized to be relate to malignant behaviors of cancer and outcomes of patients in various cancers. SLC35A2 serves as a nucleotide sugar transporter and plays an indispensable role on glycosylation. However, effects of SLC35A2 on malignant behaviors of cancer cells and alteration of cancer cells surface glycosylation profile are still not fully understood, particularly in liver cancer. Hence, from an glycosylation prospective, we assessed the effects of SLC35A2 on malignant behaviors including metastatic potential of liver cancer cells. Methods SLC35A2 expression in HCC cells was examined by Western blot and quantitative PCR and was regulated by RNA interference or vectors-mediated transfection. Effects of SLC35A2 expression alteration on malignant behaviors and membrane glycan profile of HCC cells by using respectively invasion, migration, cell adhesion assay and lectins microarray. Co-location among proteins in HCC cells was observed by fluorescence microscope and detected by an in vitro co-immunoprecipitation assay. Results SLC35A2 was upregulated in HCC, and associated with poor prognosis of patients. SLC35A2 knockdown led to the decrese of invasion, adhesion, metastasis and the alteration of membrane glycan profile as well as the dysregulated expressions or glycosylation of cell adhesion-related molecules in HCC. Mechanistically, delivery of B4GalT1 to Golgi apparatus required the involvement of SLC35A2 in HCC cells and the site G266 was critical in maintaining the intact activity of B4GalT1. Conclusion SLC35A2 plays important roles in promoting HCC metastasis by regulating glycosylation modification on HCC cell surface and inducing cell adhesive ability.