Department of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St., MC3-3320, Houston, TX 77030, USA.
Crit Rev Oncol Hematol. 2009 Dec;72(3):181-93. doi: 10.1016/j.critrevonc.2008.12.002. Epub 2009 Jan 21.
Genomic instability, aberrant cell proliferation and defects in apoptotic cell death are critical issues in cancer. The two most prominent hallmarks of cancer cells are multiple mutations in key genes encoding proteins that regulate important cell-survival pathways, and marked restructuring or redistribution of the chromosomes (aneuploidy) indicative of genomic instability. Both these aspects have been suggested to cause cancer, though a causal role for chromosomal restructuring in tumorigenesis has not been experimentally fully substantiated. This review is aimed at understanding the mechanisms of cell cycle (proliferation) and programmed cell death (apoptosis) and chromosomal instability governed by cohesin and other aneuploidy promoters, which will provide new insights into the process of carcinogenesis and new avenues for targeted treatment.
基因组不稳定性、异常细胞增殖和细胞凋亡缺陷是癌症的关键问题。癌细胞的两个最显著特征是编码调节重要细胞存活途径的蛋白质的关键基因的多种突变,以及指示基因组不稳定性的染色体结构重排或重新分布(非整倍体)。这两个方面都被认为是导致癌症的原因,尽管染色体结构重排在肿瘤发生中的因果作用尚未在实验上得到充分证实。本综述旨在了解由黏合蛋白和其他非整倍体促进子控制的细胞周期(增殖)和程序性细胞死亡(凋亡)以及染色体不稳定性的机制,这将为癌变过程提供新的见解,并为靶向治疗开辟新的途径。