Identifying causes and consequences of centrosome amplification in cancer

项目摘要/摘要 癌症是美国第二大死因，迫切需要新的治疗方法。 中心体是细胞微管组织中心，对细胞的忠实分裂很重要 染色体在有丝分裂过程中，通常在癌症中调节失调。大多数人类肿瘤都有带有 中心体放大，或中心体数量异常增加。作为中心体的结果 在扩增过程中，癌细胞可能经历不对称的细胞分裂，导致染色体不稳定和 非整倍体，这是允许癌症进化和逃避治疗的基因多样性的来源。然而，它 目前尚不清楚中心体扩增是如何发生的，它如何影响患者的预后，以及它如何影响迁移 和转移潜能。 这项拟议的研究的首要目标是了解中心体在癌症中是如何失调的。 并调查随后的细胞和临床后果。本文提出的研究将 加强我们对癌症中心体扩增，特别是癌细胞分裂和迁移的认识， 并有可能找到以中心体扩增为靶点的癌细胞的新方法。

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.