Powell Anne E, Shung Chia-Yi, Saylor Katherine W, Müllendorff Karin A, Weiss Joseph B, Wong Melissa H
Department of Cell and Developmental Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Stem Cell Res. 2010 Jan;4(1):3-9. doi: 10.1016/j.scr.2009.09.005. Epub 2009 Sep 25.
Asymmetric stem cell division has emerged as a major regulatory mechanism for physiologic control of stem cell numbers. Reinvigoration of the cancer stem cell theory suggests that tumorigenesis may be regulated by maintaining the balance between asymmetric and symmetric cell division. Therefore, mutations affecting this balance could result in aberrant expansion of stem cells. Although a number of molecules have been implicated in regulation of asymmetric stem cell division, here, we highlight known tumor suppressors with established roles in this process. While a subset of these tumor suppressors were originally defined in developmental contexts, recent investigations reveal they are also lost or mutated in human cancers. Mutations in tumor suppressors involved in asymmetric stem cell division provide mechanisms by which cancer stem cells can hyperproliferate and offer an intriguing new focus for understanding cancer biology. Our discussion of this emerging research area derives insight from a frontier area of basic science and links these discoveries to human tumorigenesis. This highlights an important new focus for understanding the mechanism underlying expansion of cancer stem cells in driving tumorigenesis.
不对称干细胞分裂已成为一种对干细胞数量进行生理控制的主要调节机制。癌症干细胞理论的复兴表明，肿瘤发生可能通过维持不对称和对称细胞分裂之间的平衡来调节。因此，影响这种平衡的突变可能导致干细胞异常扩增。尽管有许多分子参与了不对称干细胞分裂的调节，但在此，我们着重介绍在这一过程中具有既定作用的已知肿瘤抑制因子。虽然这些肿瘤抑制因子中的一部分最初是在发育背景中定义的，但最近的研究表明它们在人类癌症中也会缺失或发生突变。参与不对称干细胞分裂的肿瘤抑制因子中的突变提供了癌症干细胞能够过度增殖的机制，并为理解癌症生物学提供了一个有趣的新焦点。我们对这一新兴研究领域的讨论从基础科学的前沿领域获得了见解，并将这些发现与人类肿瘤发生联系起来。这突出了一个重要的新焦点，即理解癌症干细胞扩增在驱动肿瘤发生中的潜在机制。
