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

EML 4-ALK变体3结合并稳定微管。它还将有丝分裂激酶NEK 9和NEK 7募集到微管，并且有多项研究表明这些激酶影响微管组织，例如通过Eg 5的磷酸化。因此，我们假设表达EML 4-ALK V3而非V1的肺癌细胞表现出改变的有丝分裂纺锤体组织、有丝分裂进展和潜在的SAC控制。本项目的目的是检验表达EML 4-ALK变体3的细胞由于有丝分裂进程受到干扰而表现出对抗有丝分裂治疗药物敏感性改变的假设。这将通过以下方式进行研究：检查EML 4-ALK变体在间期和有丝分裂中的定位3检查表达EML 4-ALK变体的细胞中的有丝分裂纺锤体组织和潜在的中心体扩增3检查EML 4-ALK变体的表达是否改变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