Epithelial to mesenchymal transition (EMT) is an important program in tumour progression that has been shown to facilitate cancer cell survival, chemoresistance and metastasis. The identification of novel metastatic mediators that are central to the EMT process may represent unique and improved therapeutic targets for metastatic disease. The FK506 binding proteins (FKBPs) are a family of proteins that have been identified in the progression of cancers, including that of breast cancer. Specifically, an FKBP family member, known as FKBP25, has been demonstrated to play a role in cytoskeletal dynamics, p53 regulation, and nucleic acid handling which are linked with the EMT process.
Upon examination of a panel of breast cancer cell lines, ranging from epithelial-like to mesenchymal, we determined a distinct pattern of FKBP25 expression. Specifically, mesenchymal cells expressed lower levels of FKBP25 than epithelial-like cell lines. Furthermore, in an epidermal growth factor mediated model of EMT using MDA-MB-468 cells, it was found that FKBP25 levels were decreased as the cells transitioned to a mesenchymal phenotype. This data suggests that the loss of FKBP25 may be required for EMT. Considering this, we aimed to assess the impact of FKBP25 knockdown on MDA-MB-468 cell invasion, proliferation and migration.
To determine the impact of FKBP25 on cell function we subjected the knockdown cell line to a variety of in vitro assays. Contrary to our hypothesis, it was found that there were no changes to invasion outgrowth, and a reduction in colony formation. However, it was observed that FKBP25 knockdown resulted in an increase in cell numbers over time suggesting an increase in proliferation and/or a decrease in cell death. FKBP25 is a known cytoskeletal stabiliser, thus the loss of FKBP25 may improve cytoskeletal dynamics involved in proliferation. To support this, we are currently extending our investigations to assess the effects of FKBP25 knockdown on migration and chemotaxis.