title: S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer.
abstract: S100A16 is a member of the S100 calcium-binding protein family. It is overexpressed in many types of tumors and associated with proliferation, migration, and invasion; however, its function in human prostate cancer is unresolved. Our objective was to determine its effects and the underlying pathways of S100A16 in prostate cancer tissues and cells. We measured S100A16 expression by quantitative real-time polymerase and Western blotting in eight matched prostate cancer and adjacent normal tissues, and in three prostate cancer cell lines, DU-145, LNCaP, and PC-3, compared to a normal prostate epithelial cell line PrEC. DU-145 cells stably overexpressing S100A16 and PC-3 cells with S100A16 knockdown were established by transfection with S100A16 overexpression plasmid or shRNAs. Invasion, migration, and proliferation were analyzed by transwell assay, wound healing, and colony formation assays, respectively. Western blotting and invasion assays were performed to determine expressions and activation of AKT, ERK, p21, and p27. S100A16 was significantly overexpressed in both prostate cancer tissues and cells lines compared to normal controls (P < 0.05). Overexpression of S100A16 significantly promoted invasion, migration, and proliferation in prostate cancer cells in vitro, whereas silencing S100A16 showed the converse effects (P < 0.05). Furthermore, overexpression of S100A16 activated cell signaling proteins AKT and ERK and downregulated tumor suppressors p21 and p27. Specific inhibitors, LY294002 and PD98059, suppressed activation of AKT and ERK, which attenuated DU-145 cell clone formation and invasion induced by S100A16 overexpression. S100A16 may promote human prostate cancer progression via signaling pathways involving AKT, ERK, p21, and p27 downstream effectors. Our findings suggest that S100A16 may serve as a novel therapeutic or diagnostic target in human prostate cancer.
authors.affiliation: Department of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, 210008, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Urology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Rihua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Su
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Xiubin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Menglan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, 210029, China. azzhao30@gmail.com.
authors.forename: Allan Z
authors.initials: AZ
authors.lastname: Zhao
authors.affiliation: Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. dr_liuyun@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009418:S100 Proteins; C000589580:S100A16 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt
keywords: Invasion; Migration; PI3K/AKT and MAPK/ERK; Proliferation; Prostate cancer; S100A16; Signaling