Summary
Signal transduction networks are critical in determining cell fate during development and when mutated are causative in tumor formation and metastasis. One of the hallmarks of cell differentiation in the colon is the induction of cell polarity and brush border formation. Importantly, in tumor cells this polarity is mostly lost. We have previously identified a cell autonomous mechanism of cell polarisation and brush border formation in colon cell lines. This mechanism includes the activation of the kinase LKBStrad. In this project we aim to determine the signalling network that is mediating LKBStrad- induced polarity and brush border formation by quantitative mass spec analysis using SILAC. In addition we will investigate whether these networks also function during the in vitro differentiation of primary colon stem cells. For that purpose we will isolate stem cells from in vivo 13C6-leucine-labeled mice for quantitative proteomic analysis
We anticipate that this study will reveal key components in the signalling network that induces cell polarity and brush border formation in the colon.