title: INPP4B is an oncogenic regulator in human colon cancer.
abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
authors.forename: S T
authors.initials: ST
authors.lastname: Guo
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: M N
authors.initials: MN
authors.lastname: Chi
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
authors.forename: R H
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Guo
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital and Institute, Shanxi, China.
authors.forename: L K
authors.initials: LK
authors.lastname: Zan
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital and Institute, Shanxi, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Xi
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Croft
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Tseng
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: X G
authors.initials: XG
authors.lastname: Yan
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Farrelly
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
authors.forename: F H
authors.initials: FH
authors.lastname: Wang
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Lai
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital and Institute, Shanxi, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Shanxi Cancer Hospital and Institute, Shanxi, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ackland
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Scott
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Miami, FL, USA.
authors.forename: I U
authors.initials: IU
authors.lastname: Agoulnik
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Hondermarck
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: R F
authors.initials: RF
authors.lastname: Thorne
authors.affiliation: Children's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: X D
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Jiang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism
chemical_list: D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase