The crosstalk between cell signaling and cell resistance in Triple Negative Breast Cancer

Triple Negative Breast Cancer (TNBC) is the most lethal molecular subtype of breast cancer according to a huge heterogeneity, aggressive behavior, and lack of selective treatment strategies. Chemotherapy is the only option available to treat this type of disease, and, unfortunately, chemoresistance is an early and frequent phenomenon in a process that is still largely unknown. The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in migration, invasion, metastasis, and stem cell renewal in various types. Preliminary results from our group suggest that TNBC chemoresistance could also be acquired by Wnt stimuli, where the Wnt-response enhances a stem-like and low proliferative cellular state. These results also suggest cells are going in apoptosis could be involved in releasing of extracellular biomolecules that enhance and/or activate Wnt pathway spreading the resistance features. Since quiescence and stemness are known as major drivers of resistance and recurrence, a deeper knowledge of how apoptosis and Wnt are involved in these processes and so in the chemoresistance, is needed. Combining data from cell-derived xenografts, patient-derived xenografts (PDXs), and patient datasets, with particular attention to transcriptomic and proteomics analysis, we aim to understand the link among chemotherapy, apoptosis, Wnt- signaling and (chemo-)resistance.