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Identifying causes and consequences of centrosome amplification in cancer

确定癌症中心体扩增的原因和后果

基本信息

批准号：
9534556
负责人：
RYAN Austin DENU
金额：
$ 3.67万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9534556
关键词：
Address Affect Aneuploidy Breast Cancer Patient Cause of Death Cell Line Cell division Cell fusion Cell physiology Cells Cellular Structures Centrioles Centrosome Chromosomal Instability Chromosomes Cilia Ciliary Motility Disorders Clinical Coupled Cytokinesis Defect Disease Drug Targeting Enzymes Epigenetic Process Failure Gene Mutation Genes Genetic Materials Genetic Variation Goals Growth Human Induced Mutation Interphase Knowledge Lead Learning Malignant Neoplasms Mass Spectrum Analysis Mediating Microcephaly Microtubule-Organizing Center Microtubules Mitosis Mitotic spindle Molecular Mutate Mutation Outcome PLK1 gene Pathway interactions Patient-Focused Outcomes Phenotype Polycystic Kidney Diseases Positioning Attribute Prevalence Process Prognostic Factor Proliferating Proteins Regulation Reporting Research Retinal Diseases Role Shapes Signal Transduction Source Testing Tetracyclines Tissue Microarray Variant cancer cell cancer type cell behavior cell motility chemical genetics genetic approach human disease improved insight malignant breast neoplasm migration neoplastic cell novel novel therapeutics overexpression phosphoproteomics prognostic prognostic value protein complex rho GTP-Binding Proteins therapeutic target tumor

项目摘要

PROJECT SUMMARY / ABSTRACT Cancer is the second leading cause of death in the U.S., and novel therapeutics are of great need. Centrosomes are cellular microtubule organizing centers that are important for the faithful division of chromosomes during mitosis and are commonly dysregulated in cancer. Most human tumors have cells with centrosome amplification, or an abnormally elevated number of centrosomes. As a result of centrosome amplification, cancer cells can undergo asymmetric cell division, leading to chromosomal instability and aneuploidy, which is a source of genetic diversity that allows cancer to evolve and evade therapies. However, it is unclear how centrosome amplification arises, how it affects patient outcomes, and how it affects migration and metastatic potential. The overarching goal of this proposed research is to understand how centrosomes are dysregulated in cancer and to investigate the subsequent cellular and clinical consequences. The research proposed herein will enhance our knowledge of centrosome amplification in cancer, especially cancer cell division and migration, and potentially identify novel ways to target cancer cells with centrosome amplification.

项目总结/摘要癌症是美国第二大死亡原因，和新的治疗方法是非常需要的。中心体是细胞微管的组织中心，对于细胞的忠实分裂非常重要。染色体在有丝分裂期间，并且通常在癌症中失调。大多数人类肿瘤的细胞中心体扩增或中心体数目异常升高。由于中心体扩增，癌细胞可以经历不对称的细胞分裂，导致染色体不稳定性，非整倍体，这是遗传多样性的来源，允许癌症进化和逃避治疗。但目前尚不清楚中心体扩增是如何产生的，它如何影响患者的结果，以及它如何影响迁移和转移潜能。这项研究的首要目标是了解中心体在癌症中是如何失调的并研究随后的细胞和临床后果。本文提出的研究将提高我们对癌症中心体扩增的认识，特别是癌细胞分裂和迁移，并有可能发现利用中心体扩增靶向癌细胞的新方法。