title: ST6Gal-I overexpression facilitates prostate cancer progression via the PI3K/Akt/GSK-3β/β-catenin signaling pathway.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Anwen
authors: A
authors: Wei
authors: Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China.
authors: Bo
authors: B
authors: Fan
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Yujie
authors: Y
authors: Zhao
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Han
authors: H
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Liping
authors: L
authors: Wang
authors: Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Xiao
authors: X
authors: Yu
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Qingmin
authors: Q
authors: Yuan
authors: Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China.
authors: Deyong
authors: D
authors: Yang
authors: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors: Shujing
authors: S
authors: Wang
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008297:Male; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D012799:Sialyltransferases; D051176:beta Catenin; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: 6-sialic acid; ST6Gal-I; prognosis; proliferation and invasion; prostate cancer; α2