LKB1 - linking the regulation of cell polarity to cell proliferation control in physiological state and cancer

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The establishment and maintenance of cell polarity is one of the most important issues in multicellular organisms. Notably, many key factors regulating cell polarity are also implicated in the control of cell proliferation and growth inhibition, which are strongly impaired in transformed cells. The tumour sup-pressor LKB1 has been shown to be involved in both processes – regulation of cell polarity and control of cell proliferation. Although some studies have already provided evidence about several processes in which LKB1 functions, it is still unclear how LKB1 itself is regulated. Further it still remains elusive which downstream effectors are crucial for its control of cell polarity and cell proliferation.Due to the fact that LKB1 as a “master kinase” is capable to activate several downstream kinases and pathways it is difficult to dissect its role in a distinct mechanism. Therefore we identified new interac-tion partners and substrates for LKB1 in the model organism Drosophila melanogaster. From the anal-ysis of the phosphorylation events of LKB1 substrates and downstream targets we aim to draw con-clusions about the mechanisms underlying LKB1 function in physiological state and cancer. Therefore we will initially use Drosophila neural stem cells and other polarized cells as model system. Obtained results will subsequently be tested in vertebrate systems.