Background/Aims: The contextual oncogene Liver Kinase B1 (LKB1/STK11) is mutated with high frequency in the common cancers. Research from O’Farrell et al. 2017 showed LKB1 localises to endosomes. My aim has been to further map the route that LKB1 takes within the cell and the significance of its localisation to its role in the cell. Are these roles passive and coincidental with LKB1 being a membrane bound protein? Or active roles that could have far-reaching effects in tumorigenesis and metastasis?

I use Drosophila melanogaster expressing a GFP-tagged LKB1 protein under control of the endogenous promoter (a slight overexpression creating a sensitized background) with knock down of a gene of interest. I then measure disc disruption, changes in LKB1 levels and changes in LKB1 localisation. Positive hits are being examined with immunolabelling to elucidate the effect on tumorigenesis/metastasis. Interesting phenotypes will be examined in lkb1 overexpression or knockdown lines also.

The screen has revealed an interaction between LKB1 and vesicle trafficking, where LKB1 has an active role and is not just ‘along for the ride’. I see a wide range of phenotypes, varying from changes in LKB1 levels and localisation to massive disc overgrowth and migratory cells. This implies a novel link between LKB1, vesicle trafficking and cancer. I am now following up my results using the human colorectal adenocarcinoma Caco-2 cell line.

As vesicle trafficking is often targeted in cancer therapies, the clarity gained by these results may aid in development of new therapies or increase efficacy of the current therapies.