Li Jing, Dallmayer Marlene, Kirchner Thomas, Musa Julian, Grünewald Thomas G P
Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Trends Cancer. 2018 Jan;4(1):59-73. doi: 10.1016/j.trecan.2017.11.002. Epub 2017 Dec 16.
Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity. We discuss targeting PRC1 within the complementary approaches of either normalizing CIN in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis.
胞质分裂是细胞周期的最后一个事件,它将一个细胞分裂为两个子细胞。胞质分裂蛋白调节剂(PRC)1对胞质分裂和正常细胞分裂至关重要。PRC1失调会导致胞质分裂缺陷,进而促进染色体不稳定(CIN),从而导致肿瘤异质性和癌症进展。同样,PRC1异常表达与多种恶性肿瘤患者的不良预后相关,这可能是由PRC1介导的CIN和非整倍体引起的。在这里,我们综述了PRC1在细胞周期调控中的生理功能及其对肿瘤发生和肿瘤内异质性的贡献。我们讨论了在非整倍体癌症中使CIN正常化或在基因组稳定的癌症中制造染色体混乱以诱导凋亡这两种互补方法中靶向PRC1的问题。