title: A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.
abstract: The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Rolando
authors.initials: R
authors.lastname: Perez-Lorenzo
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Kamraan Z
authors.initials: KZ
authors.lastname: Gill
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York, USA.
authors.forename: Che-Hung
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Feng X
authors.initials: FX
authors.lastname: Zhao
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, Fachklinik Hornheide at University Muenster, Muenster, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schulze
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Silvers
authors.affiliation: Department of Cancer Research, Fachklinik Hornheide at University Muenster, Muenster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Brunner
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, New York, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address: bh2179@cumc.columbia.edu.
authors.forename: Basil A
authors.initials: BA
authors.lastname: Horst
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014015:Tissue Banks
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human