Roles for microtubule-associated proteins in cancer cells.
Microtubules(MTs) play a fundamental role in diverse cellular functions such as cell division, motility and the trafficking of organelles and proteins. EB1 is a member of a family of MT-associated proteins conserved from yeast to man. It was first identified through its interaction with the adenomatous polyposis coli (APC) tumour suppressor protein. More recently EB1 was shown to localise to and act at centrosomes and to belong to an emerging class of MT-associated proteins that specifically localise to growing MT ends (+TIPs). One of the main interests in our laboratory is how proteins such as EB1 localise to growing MT tips and centrosomes and the role these proteins then play at these sites in mammalian cells. This could have important implications for our understanding of the cellular defects underlying the development and progression of human cancer. For example, genetic instability is a feature of many human cancers. Understanding the function of MT-associated proteins could provide important insights into how human cells ensure the fidelity of chromosomal transmission during normal cell division and help reveal the ways in which these mechanisms are circumvented in cancer.
Figure 1 Distribution of APC (green), MTs (red) and actin (blue) in a migrating MDCK epithelial cell
Figure2 EB1(red) localises to a subset of MT(green) tips.
Lee, T., Langford, K. J., Askham, et al. MCAK associates with EB1. Oncogene 2007, advance online publication Oct 29th 2007
Morrison EE. Action and interactions at microtubule ends. Cell Mol Life Sci 2006; 64, 307-317.
Langford KJ, Askham JM, Lee T et al. Examination of actin and microtubule dependent APC localisations in living mammalian cells. BMC Cell Biol 2006; 7:3.