To properly respond to growth-stimulatory and growth-inhibitory signals in their micro-environment, cells possess multiple signal transduction pathways, consisting of specific enzymes, messenger and adaptor molecules that transmit these signals from their receptors to the nucleus, where transcription factors convert them into specific gene expression programs. To be able to integrate the information from different types and doses of stimuli that can reach a cell simultaneously or within short (repeated) intervals, signaling molecules from distinct pathways interact at many levels, both on the membrane, in the cytoplasm and in the nucleus, thereby forming large molecular networks that are often localized to specific sub-cellular structures. During carcinogenesis and cancer progression cells lose their ability to correctly respond to growth inhibitory signals, and/or show increased sensitivity to growth-stimulatory and pro-invasive signals. This is the result of genetic defects, such as mutation, deletion or amplification of specific signaling molecules, or due to epigenetic events such as gene silencing.
We are interested in the detection, identification and functional characterization of signaling complexes and intermediates that distinguish cancer cells from normal cells, or that differ during the different stages of tumor progression. These complexes might function as diagnostic and/or prognostic markers and become targets for (patient-specific) therapeutic intervention.