Receptor interactions as key modulators of tumour metastatic progression: the case of MET and Plexin B1.

The epithelial-mesenchymal transition (EMT) is a key evolutionary conserved, developmental process which is hijacked by the tumour microenvironment early in the invasion-metastasis cascade. In the last three decades, the receptor tyrosine kinase MET has emerged as a fundamental molecular switch that triggers the complex set of cellular changes, which altogether lead to EMTs. More recently, MET co-receptors have come to the fore as relevant modulators of MET signaling and function in tumour progression. The primary aim of the current study was to investigate the nature of the interaction between MET and its putative co-receptor Plexin B1, with biophysical and biochemical techniques. Initial experiments by surface plasmon resonance (SPR) were carried out using soluble constructs of the MET and Plexin B1 ectodomains. We also made progress towards the generation of full length, fluorescently tagged MET and Plexin B1 for FRET-FLIM/FCCS studies. Results are critically discussed in the light of non-classical cell surface signaling, analysing the multifarious molecular determinants which could influence MET-Plexin B1 interaction in different cellular contexts and cancer types.