Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila
Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila
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与肿瘤细胞不同，野生型成体干细胞能够抵抗果蝇中的细胞损伤
DOI：
10.1016/j.ydbio.2016.01.040
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发表时间：
2016-03-15
影响因子：
2.7
通讯作者：
Li, Zhouhua
中科院分区：
文献类型：
--
作者：
Ma, Meifang;Zhao, Hang;Li, Zhouhua
成体干细胞或成体祖细胞对于在个体一生中维持成体组织的结构和功能(内稳态)至关重要。干细胞增殖和分化的错误调控经常导致包括癌症在内的疾病，然而，野生型成体干细胞和癌细胞如何应对细胞损伤仍不清楚。我们发现，在成年果蝇中肠中，肠干细胞(ISCs)与肿瘤肠道细胞不同，对各种细胞损伤具有抵抗力。与野生型ISCs不同，肿瘤肠道细胞很容易被凋亡消除。此外，它们的增殖在自噬诱导时被抑制，并且自噬介导的肿瘤抑制不依赖于caspase依赖的凋亡。有趣的是，自噬对肿瘤发生的抑制可能是通过线粒体的隔离和降解来实现的，因为在这些肿瘤模型中，线粒体活性的降低模仿了自噬的诱导，而线粒体的增加减轻了自噬的肿瘤抑制能力。总之，这些数据表明，野生型成体干细胞和肿瘤细胞对细胞损伤的敏感性存在显著差异，从而提供了针对肿瘤发生的潜在治疗意义。(C)2016 Elsevier Inc.保留所有权利。
Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis. (C) 2016 Elsevier Inc. All rights reserved.