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

研究 EML4-ALK 融合蛋白在非小细胞肺癌有丝分裂进展中的作用

• 批准号: 1898566
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1898566
• 关键词: Investigating; role; EML4; ALK; fusion

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

EML4-ALK变体3结合并稳定微管。它还招募有丝分裂激酶NEK9和NEK7到微管，有多项研究表明这些激酶影响微管组织，例如通过磷酸化Eg5。因此，我们假设表达EML4-ALK V3而不表达V1的肺癌细胞表现出有丝分裂纺锤体组织、有丝分裂进程和潜在的SAC控制的改变。这可能使它们对抗有丝分裂疗法敏感。这个项目的目的是验证一个假设，即表达EML4-ALK变体3的细胞对抗有丝分裂治疗药物的敏感性由于有丝分裂进程受到干扰而改变。这将通过以下方法进行研究：检查EML4-ALK变体在间期和有丝分裂中的定位；检查表达EML4-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；检查EML4-ALK变体的表达是否改变纺锤体组装检查点的完整性