Centers for Cancer Research, Regenerative Medicine, Human Genetics Research, and Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12845-50. doi: 10.1073/pnas.1109632108. Epub 2011 Jul 14.
Human tumors often contain slowly proliferating cancer cells that resist treatment, but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating "G0-like" progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small-molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur.
人类肿瘤通常含有对治疗有抵抗力的缓慢增殖癌细胞，但我们并不清楚这些细胞究竟是如何产生的。我们发现，快速增殖的癌细胞能够不对称分裂，产生对化疗药物有抵抗性的“G0 样”子细胞，而这种子细胞在乳腺癌患者中更为富集。不对称的癌细胞分裂源于有丝分裂末期一个子细胞中 AKT/PKB 激酶信号的不对称抑制。此外，用小分子药物抑制 AKT 信号能够诱导不对称的癌细胞分裂，并产生增殖缓慢的细胞。因此，癌细胞似乎能够根据 AKT 信号网络的精确状态，在对称分裂和不对称分裂之间持续转换。这个模型可能对理解肿瘤如何生长、逃避治疗以及复发具有重要意义。
