YB-1 affects response to paclitaxel in TNBCs by modulation of EGR1

For patients with triple negative breast tumours (TNBCs), lacking receptors for oestrogen, progesterone or HER2 on their cell surface, chemotherapy is the main treatment. The taxanes, paclitaxel (PTX) and docetaxel, have become the most commonly-used chemotherapies for these kinds of breast cancer. Although several targeted therapies are currently undergoing clinical trials for TNBC, because of the heterogeneous nature of TNBCs, it is predicted that these may often be used in combination with chemotherapy. Therefore an understanding of the mechanisms of chemotherapy resistance will continue to be important for the treatment of these patients. Given the pleiotropic nature of YB-1, the aim of this study was to understand whether there were mechanisms in addition to those discussed above, by which YB-1 controls response to PTX in TNBCs. We initially followed up two previously studied mechanisms, mediated by ABCB1/MDR1 and DUSP4. We then proceeded to use genomics to identify novel mechanisms by which YB-1 regulates the response of TNBCs to PTX. This analysis identified and experimentally validated EGR1, encoding the early growth response protein 1 (EGR1) as a previously undiscovered mechanism of YB-1-driven PTX resistance.