Investigating the role of EML4-ALK fusion proteins in mitotic progression of non-small cell lung cancer

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EML4-ALK variant 3 binds and stabilises microtubules. It also recruits the mitotic kinases, NEK9 and NEK7, to microtubules and there are multiple studies to show that these kinases influence microtubule organization, e.g. through phosphorylation of Eg5. Hence, we hypothesise that lung cancer cells expressing EML4-ALK V3, but not V1, exhibit altered mitotic spindle organization, mitotic progression and, potentially, SAC control. This could render them sensitive to anti-mitotic therapeutics.The aim of this project is to test the hypothesis that cells expressing EML4-ALK variant 3 exhibit altered sensitivity to anti-mitotic therapeutic agents as a result of perturbed mitotic progression. This will be investigated by:Examining the localisation in interphase and mitosis of EML4-ALK variant 3Examining mitotic spindle organisation and potential centrosome amplification in cells expressing EML4-ALK variant 3Examining whether the expression of EML4-ALK variants alters integrity of the spindle assembly checkpoint