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

EML4-ALK变异体3结合并稳定微管。它还招募有丝分裂酶NEK9和NEK7进入微管，有多项研究表明，这些激酶影响微管组织，例如通过EG5的磷酸化。因此，我们假设表达EML4-ALK V3的肺癌细胞，而不是表达V1的肺癌细胞，表现出改变的有丝分裂纺锤体结构、有丝分裂进程以及潜在的SAC控制。这可能使它们对抗有丝分裂治疗敏感。本项目的目的是检验这样的假设，即表达EML4-ALK变体3的细胞由于有丝分裂进程受扰而对抗有丝分裂治疗药物的敏感性发生改变。这将通过以下方式进行研究：检查EML4-ALK变体在间期和有丝分裂中的定位3检查表达EML4-ALK变体的细胞中有丝分裂的纺锤体组织和潜在的中心体放大3检查EML4-ALK变体的表达是否改变了纺锤体组装检查点的完整性

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