Overexpression of the pp32r1 (ANP32C) oncogene or its functional mutant pp32r1Y140H confers enhanced resistance to FTY720 (Finguimod)

Cancer Biology & Therapy
Salma BuddasethTrevor Huyton

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.

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Citations

Jun 27, 2015·Biochimica Et Biophysica Acta·Yuliia YuzefovychTrevor Huyton
Apr 14, 2015·BioMed Research International·Shanshan WangDajin Zhang
Aug 27, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Patrick T ReillyLishun Wang
Apr 2, 2016·Oncotarget·Christopher WhiteDmitri Pchejetski

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