Identification and characterisation of pro-metastatic targets, pathways and molecular complexes using a toolbox of...

Cancer metastasis involves changes in signalling pathways, cell adhesion, migration and invasiveness. Modern proteomic, mass spectrometry based techniques enable discovery of new pro-metastatic proteins and their functional partners. Also, they might be involved in their functional characterisation and validation towards development of new diagnostic and therapeutic approaches.

The aim of this communication is to describe current possibilities for proteomic techniques in the discovery and characterization of pro-metastatic targets. The NF-kappaB pathway is one of the players responsible for a number of pro-metastatic processes. The related proteins can be discovered using untargeted proteomic approaches by comparing proteomes with different metastatic potential. Stable isotope labelling based methods enable a parallel analysis of more tumour samples. The identified pro-metastatic proteins can be characterised in relationship to cell migration, invasiveness and proliferation and in terms of their involvement in molecular complexes via protein-protein interactions. Advantages of the metabolic labelling based methods can be taken in these studies, the same applies for characterisation of related surface proteins involved in cell adhesion, invasiveness and cell-to-cell communication. For clinical validation of pro-metastatic proteins in large sample cohorts, approaches of targeted proteomics based on selected reaction monitoring are becoming methods of choice.

Current proteomics methods play an important role in the identification of novel pro-metastatic proteins, pathways and molecular complexes, in their functional characterisation and validation towards diagnostic and therapeutic application.