In vivo analysis of the role of EMT in triple-negative breast cancer initiation and immune modulation.

01 November 2019 → 31 October 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Cancer biology
    • Cancer therapy
breast cancer
Project description

Triple-negative breast cancers (TNBCs), which are negative for both hormone and HER2 receptors, represent approximately 10-20% of the BC cases and are characterized by a poor prognosis with limited therapeutic options. TNBC is a heterogeneous disease that can be subdivided based on molecular characteristics into multiple subtypes, including the basal-like (BL) and claudin-low (CL) subtypes. TNBC has been associated with epithelial-to-mesenchymal transition (EMT), a process in which cells loose the capacity to adhere to one another and become motile. ZEB1, a potent EMT-transcription factor, is often upregulated in TNBC and associated with poor prognosis in these patients. We identified ZEB1 as an important factor in the etiology of basal-like BC. The aim of this project is to identify pathways that collaborate with ZEB1 in the malignant transformation of basal-like breast cancer. As many TNBCs show high infiltration of immune cells, we will also examine how EMT contributes in the crosstalk between immune and cancer cells and address if this is important for the malignant behaviour of cancer cells in models of BL and CL BC. Furthermore, on the basis of our findings we will study potential novel combinatorial therapy options to optimize immunotherapy for BL and CL subtypes of BC. Ultimately, our research should make clear if targeting EMT or activating signalling pathways would result in impairment of the malignant behaviour of BC cells and sensitize them for immunotherapy.