Abstract:
Asymmetric cell division (ACD) gives rise to two daughter cells with different fates after mitosis and is a fundamental process for generating cell diversity and for the maintenance of the stem cell population. The cancer stem cell (CSC) theory suggests that CSCs with dysregulated self-renewal and asymmetric cell division serve as a source of intra-tumoral heterogeneity. This heterogeneity complicates the diagnosis and treatment of cancer patients, because CSCs can give rise to aggressive clones that are metastatic and insensitive to multiple drugs, or to dormant tumor cells that are difficult to detect. Here, we review the regulatory mechanisms and biological significance of asymmetric division in tumor cells, with a focus on ACD-induced tumor heterogeneity in early tumorigenesis and cancer progression. We will also discuss how dissecting the relationship between ACD and cancer may help us find new approaches for combatting this heterogeneity.
摘要:
不对称细胞分裂(ACD)在有丝分裂后产生具有不同命运的两个子细胞,是产生细胞多样性和维持干细胞群的基本过程。癌症干细胞(CSC)理论表明,自我更新失调和不对称细胞分裂的CSC是肿瘤内异质性的来源。这种异质性使癌症患者的诊断和治疗复杂化,因为CSC可以产生侵袭性克隆,这些克隆是转移性的,对多种药物不敏感,或难以检测的休眠肿瘤细胞。这里,本文综述了肿瘤细胞不对称分裂的调控机制和生物学意义,重点关注ACD诱导的早期肿瘤发生和癌症进展中的肿瘤异质性。我们还将讨论如何解剖ACD和癌症之间的关系可以帮助我们找到新的方法来对抗这种异质性。