ST6Gal-I overexpression facilitates prostate cancer progression via the PI3K/Akt/GSK-3?/?-catenin signaling pathway.

ABSTRACT: ST6Gal-I sialyltransferase adds ?2,6-linked sialic acids to the terminal ends of glycan chains of glycoproteins and glycolipids. ST6Gal-I is reportedly upregulated in many cancers, including hepatocellular carcinoma, ovarian cancer and breast cancer. However, the expression and function of ST6Gal-I in prostate cancer (PCa) and the mechanism underlying this function remain largely unknown. In this study, we observed that ST6Gal-I expression was upregulated in human PCa tissues compared to non-malignant prostate tissues. High ST6Gal-I expression was positively correlated with Gleason scores, seminal vesicle involvement and poor survival in patients with PCa. ST6Gal-I knockdown in aggressive prostate cancer PC-3 and DU145 cells significantly inhibited the proliferation, growth, migration and invasion capabilities of these cells. ST6Gal-I knockdown decreased the levels of several PI3K/Akt/GSK-3?/ ?-catenin pathway components, such as p-PI3K, (Ser473)p-Akt, (Ser9)p-GSK-3? and ?-catenin. Furthermore, targeting this pathway with a PI3K inhibitor or Akt RNA interference decreased p-Akt, p-GSK-3? and ?-catenin expression, resulting in decreased PC-3 and DU145 proliferation, migration and invasion. Taken together, these results indicate that ST6Gal-I plays a critical role in cell proliferation and invasion via the PI3K/Akt/GSK-3?/?-catenin signaling pathway during PCa progression and that it might be a promising target for PCa prognosis determination and therapy.

SUBMITTER: Wei A 

PROVIDER: S-EPMC5323162 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature