Institute of Clinical Sciences, School of Biomedical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Int J Mol Sci. 2021 Sep 7;22(18):9667. doi: 10.3390/ijms22189667.
In principle, an oncogene is a cellular gene (proto-oncogene) that is dysfunctional, due to mutation and fusion with another gene or overexpression. Generally, oncogenes are viewed as deregulating cell proliferation or suppressing apoptosis in driving cancer. The cancer stem cell theory states that most, if not all, cancers are a hierarchy of cells that arises from a transformed tissue-specific stem cell. These normal counterparts generate various cell types of a tissue, which adds a new dimension to how oncogenes might lead to the anarchic behavior of cancer cells. It is that stem cells, such as hematopoietic stem cells, replenish mature cell types to meet the demands of an organism. Some oncogenes appear to deregulate this homeostatic process by restricting leukemia stem cells to a single cell lineage. This review examines whether cancer is a legacy of stem cells that lose their inherent versatility, the extent that proto-oncogenes play a role in cell lineage determination, and the role that epigenetic events play in regulating cell fate and tumorigenesis.
原则上，癌基因是一种细胞基因（原癌基因），由于突变和与另一个基因融合或过度表达而失去功能。通常，癌基因被视为通过调节细胞增殖或抑制细胞凋亡来驱动癌症。癌症干细胞理论指出，大多数（如果不是全部）癌症是一种细胞层次结构，它起源于转化的组织特异性干细胞。这些正常的对应物产生组织的各种细胞类型，这为癌基因如何导致癌细胞的混乱行为增添了一个新的维度。正是干细胞，如造血干细胞，通过补充成熟的细胞类型来满足生物体的需求。一些癌基因似乎通过限制白血病干细胞到单一细胞谱系来调节这种体内平衡过程。这篇综述探讨了癌症是否是干细胞失去内在多功能性的遗留物，原癌基因在细胞谱系决定中所起的作用，以及表观遗传事件在调节细胞命运和肿瘤发生中的作用。
