1) Defining the role of tetraspanin proteins in responses of breast cancer cells to ERbB2-based therapies
ErbB2/HER-2 is a member of the family of epidermal growth factor receptors. When overexpressed (e.g. in 15-25% of breast cancers), ErbB2 forms spontaneous homo- and heterodimers, which can drive tumour cell proliferation and metastasis. Although targeting ErbB2-dependent pathway with Herceptin/Trastuzumab (humanized anti-ErbB2 mAb) and Lapatinib (a small molecule tyrosine kinase inhibitor), has proven to be effective in ErbB2-overexpressing breast cancer patients, a significant proportion of them do not (or only partially) respond to the treatment.
We develop a model system in vitro to investigate how transmembrane proteins of the tetraspanin superfamily regulate responses of breast cancer cells to Herceptin and Lapatinib. Understanding molecular pathways which link the activity of tetraspanin complexes with ErbB2 will help to identify novel drug targets and develop a more effective protocol for the treatment of ErbB2-positive patients.
2) Mechanisms of EphrinB2-driven signalling in breast cancer
Bidirectional Eph-Ephrin signalling axis controls tissue differentiation and normal organ homeostasis. Abnormal activation of Eph – and Ephrin-dependent signalling is also a critical factor in tumourigenesis and metastasis. We investigate signalling mechanisms which regulate trafficking of activated EphrinB molecules in breast cancer cells and how this affects growth of cells inside three dimensional extracellular matrices.
3) Tetraspanin proteins and endocytic trafficking of associated proteins in breast cancer cells
Endocytic trafficking of transmembrane receptors controls intracellular signalling network and determines responses of breast cancer cells to extracellular environment. We study the composition and assembly of tetraspanin-based protein complexes which influence endocytic trafficking routes of transmembrane receptors.