title: Overexpression of the pp32r1 (ANP32C) oncogene or its functional mutant pp32r1Y140H confers enhanced resistance to FTY720 (Finguimod).
abstract: pp32r1 (ANP32C) is oncogenic and has been shown to be overexpressed in tumors of the breast, prostate, and pancreas. In this work we show that pp32 family proteins are able to bind to the sphingosine analog FTY720 (Finguimod). Molecular docking studies highlight that a conserved residue F136 is likely to be a key determinant of the FTY720 binding site on the pp32 leucine-rich repeat domain. Transduction of the renal carcinoma cell line ACHN or cervical cancer cell line HeLa with lentivirus expressing the oncogenic family member pp32r1 or a pp32r1Y140H functional mutant illustrated an enhanced resistance to FTY720 induced apoptosis. These findings highlight that certain cancers overexpressing pp32r1 or pp32r1 mutants are likely to demonstrate enhanced resistance to FTY720 treatment.
authors: Institute for Transfusion Medicine; Hannover Medical School; Hannover, Germany.
authors: Salma
authors: S
authors: Buddaseth
authors: Institute for Transfusion Medicine; Hannover Medical School; Hannover, Germany.
authors: Wiebke
authors: W
authors: Göttmann
authors: Institute for Transfusion Medicine; Hannover Medical School; Hannover, Germany.
authors: Rainer
authors: R
authors: Blasczyk
authors: Institute for Transfusion Medicine; Hannover Medical School; Hannover, Germany.
authors: Trevor
authors: T
authors: Huyton
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000068876:Fingolimod Hydrochloride; D005822:Genetic Vectors; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics; D062105:Molecular Docking Simulation; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014161:Transduction, Genetic
chemical_list: C489949:ANP32C protein, human; D007166:Immunosuppressive Agents; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: FTY720; cancer; cell cycle; pp32