ST6Gal-I overexpression facilitates prostate cancer progression via the PI3K/Akt/GSK-3β/β-catenin signaling pathway
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Anwen Wei1,*, Bo Fan2,*, Yujie Zhao1, Han Zhang1, Liping Wang1, Xiao Yu3, Qingmin Yuan1, Deyong Yang2, Shujing Wang1
1Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China
2Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China
3Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China
*These authors contributed equally to this work
Shujing Wang, email: firstname.lastname@example.org
Deyong Yang, email: email@example.com
Keywords: ST6Gal-I, α2,6-sialic acid, prostate cancer, prognosis, proliferation and invasion
Received: March 01, 2016 Accepted: August 24, 2016 Published: August 30, 2016
ST6Gal-I sialyltransferase adds α2,6-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-3β/ β-catenin pathway components, such as p-PI3K, (Ser473)p-Akt, (Ser9)p-GSK-3β and β-catenin. Furthermore, targeting this pathway with a PI3K inhibitor or Akt RNA interference decreased p-Akt, p-GSK-3β and β-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-3β/β-catenin signaling pathway during PCa progression and that it might be a promising target for PCa prognosis determination and therapy.
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