Differential expression of the protein phosphatase 2 (PP2A) inhibitors following PP2A activation by FTY720 in specific breast cancer cell lines

Abstract

Background: Triple negative breast cancer (TNBC) patients derive little benefit from target-specific therapies due to lack of the favourable prognostic targets oestrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor type 2 (HER2). Data from the cBioPortal and The Cancer Genome Atlas (TCGA) demonstrate that PP2A function is likely to be reduced in up to 60% of basal breast tumours. PP2A is vital tumour suppressor that regulates cell proliferation and cell survival. Tumours exhibit either homozygous deletion or underexpression of PP2A, but also overexpression of PP2A inhibitors namely CIP2A, IGBP1, ANP32A, SET and/or SETBP1. In this study we assessed the effect of FTY720, an activator of PP2A, on the viability of breast cancer cell lines. The viability is then correlated with the cellular localisation of the PP2A inhibitory subunits and the mTOR targets, phosphorylated S6K (pS6K) and phosphorylated AKT (pAKT).