The role of the AURORA-A oncogene in tumorigenesis and in the therapy response in colorectal and rectal cancer

AURORA-A 癌基因在结直肠癌肿瘤发生和治疗反应中的作用

• 批准号: 194056409
• 负责人: Professor Dr. Holger Bastians
• 金额: --
• 依托单位: Institute for Molecular Oncology
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194056409?language=en
• 关键词: role; AURORA; oncogene; tumorigenesis; therapy

The AURORA-A oncogene, located on chromosome 20q, is most frequently over-expressed in colorectal and rectal cancer. It encodes for a kinase involved in multiple steps of mitotic cell division and thus contributes to the maintenance of chromosomal stability. The most recent work has indicated that the Aurora-A protein might also be a key modulator of therapy response in human cancer, including colorectal cancer, but the underlying mechanisms are unclear. The goal of this research proposal is to elucidate the role of Aurora-A in colorectal and rectal tumorigenesis and in the response to clinically relevant therapeutic treatments. In particular, on the basis of our long-standing expertise in investigating the mechanisms of chemotherapy resistance and chromosomal instability, we will investigate how different levels of Aurora-A affect the growth of colorectal and rectal cancer in vitro and in vivo. We aim to define the molecular mechanisms of how different levels of Aurora-A in colorectal and rectal cancer modulate sensitivity toward radiotherapy and chemotherapy. Finally, we will place our results into a context of clinical data by analyzing AURORA-A expression and therapy response in primary rectal cancer samples.

AURORA-A癌基因位于染色体20q上，在结直肠癌和直肠癌中最常过度表达。它编码参与有丝分裂细胞分裂的多个步骤的激酶，因此有助于维持染色体的稳定性。最近的研究表明，Aurora-A蛋白也可能是人类癌症（包括结直肠癌）治疗反应的关键调节剂，但其潜在机制尚不清楚。本研究计划的目的是阐明Aurora-A在结直肠肿瘤发生中的作用以及对临床相关治疗的反应。特别是，在我们长期研究化疗耐药和染色体不稳定性机制的基础上，我们将研究不同水平的Aurora-A在体外和体内如何影响结直肠癌和直肠癌的生长。我们的目的是确定不同水平的Aurora-A在结直肠癌和直肠癌中如何调节对放疗和化疗的敏感性的分子机制。最后，我们将通过分析原发性直肠癌样本中AURORA-A的表达和治疗反应，将我们的结果置于临床数据的背景下。

项目成果

A phenotypic screen identifies microtubule plus end assembly regulators that can function in mitotic spindle orientation

• DOI: 10.1080/15384101.2014.1000693
• 发表时间: 2015-03-15
• 期刊: CELL CYCLE
• 影响因子: 4.3
• 作者: Stolz, Ailine;Ertych, Norman;Bastians, Holger
• 通讯作者: Bastians, Holger