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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dpp signaling and the induction of neoplastic tumors by caspase-inhibited apoptotic cells in Drosophila.
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Dpp signaling and the induction of neoplastic tumors by caspase-inhibited apoptotic cells in Drosophila.

机译：Dpp信号和果蝇中caspase抑制的凋亡细胞诱导的肿瘤性肿瘤。

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摘要

In Drosophila, stresses such as x-irradiation or severe heat shock can cause most epidermal cells to die by apoptosis. Yet, the remaining cells recover from such assaults and form normal adult structures, indicating that they undergo extra growth to replace the lost cells. Recent studies of cells in which the cell death pathway is blocked by expression of the caspase inhibitor P35 have raised the possibility that dying cells normally regulate this compensatory growth by serving as transient sources of mitogenic signals. Caspase-inhibited cells that initiate apoptosis do not die. Instead, they persist in an "undead" state in which they ectopically express the signaling genes decapentaplegic (dpp) and wingless (wg) and induce abnormal growth and proliferation of surrounding tissue. Here, using mutations to abolish Dpp and/or Wg signaling by such undead cells, we show that Dpp and Wg constitute opposing stimulatory and inhibitory signals that regulate this excess growth and proliferation. Strikingly, we also found that, when Wg signaling is blocked, unfettered Dpp signaling by undead cells transforms their neighbors into neoplastic tumors, provided that caspase activity is also blocked in the responding cells. This phenomenon may provide a paradigm for the formation of neoplastic tumors in mammalian tissues that are defective in executing the cell death pathway. Specifically, we suggest that stress events (exposure to chemical mutagens, viral infection, or irradiation) that initiate apoptosis in such tissues generate undead cells, and that imbalances in growth regulatory signals sent by these cells can induce the oncogenic transformation of neighboring cells.
机译：在果蝇中，诸如X射线照射或严重的热休克等应激可导致大多数表皮细胞因凋亡而死亡。然而，剩余的细胞从这种攻击中恢复并形成正常的成年结构，表明它们经历了额外的生长以替代丢失的细胞。对其中通过caspase抑制剂P35的表达阻断细胞死亡途径的细胞的最新研究提出了垂死的细胞通常通过充当有丝分裂信号的瞬时来源来正常调节这种代偿性生长的可能性。启动凋亡的胱天蛋白酶抑制细胞不会死亡。取而代之的是，它们以“不死”状态持续存在，在异位状态下，它们异位表达信号传导基因十足瘫痪（dpp）和无翅（wg），并诱导周围组织异常生长和增殖。在这里，我们使用突变来消除此类不死细胞的Dpp和/或Wg信号，我们显示Dpp和Wg构成了相反的刺激和抑制信号，调节了这种过度生长和增殖。令人惊讶地，我们还发现，当Wg信号被阻断时，只要胱天蛋白酶的活性在反应细胞中也被阻断，不死细胞不受束缚的Dpp信号就会将其邻居转变为赘生性肿瘤。这种现象可能为在执行细胞死亡途径方面有缺陷的哺乳动物组织中肿瘤性肿瘤的形成提供范例。具体而言，我们建议在此类组织中启动凋亡的应激事件（暴露于化学诱变剂，病毒感染或辐射）会产生不死细胞，并且这些细胞发出的生长调节信号失衡会诱导邻近细胞的致癌转化。

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