Caspases maintain tissue integrity by an apoptosis-independent inhibition of cell migration and invasion.

Caspases maintain tissue integrity by an apoptosis-independent inhibition of cell migration and invasion.
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DOI:
10.1038/s41467-018-05204-6
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发表时间:
2018-07-18
影响因子:
16.6
通讯作者:
Arama E
Arama E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gorelick-Ashkenazi A;Weiss R;Sapozhnikov L;Florentin A;Tarayrah-Ibraheim L;Dweik D;Yacobi-Sharon K;Arama E

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在发育和体内平衡期间维持组织完整性需要精确协调几个基于细胞的过程,包括细胞死亡。在动物中,大多数这样的细胞死亡通过凋亡发生,这是一种由半胱天冬酶蛋白酶介导的过程。为了阐明caspase在组织完整性中的作用,我们研究了caspase活性严重受损的果蝇上皮细胞的行为。我们表明,这些细胞获得迁移和侵入能力,无论是在1-2天内照射后或自发在发展过程中。重要的是,低水平的效应半胱天冬酶活性,这是远远低于诱导细胞凋亡所需的阈值,可以有效地抑制这一过程,以及一个独特的,原始生殖细胞迁移的发展模式。这些发现可能对癌症治疗中的放射疗法有影响。此外,由于存在的半胱天冬酶整个后生动物,我们的研究结果可能意味着,防止不必要的细胞迁移构成了一个古老的非凋亡功能的这些蛋白酶。除了调节程序性细胞死亡外,半胱天冬酶还具有非凋亡作用。在这里,作者表明,低水平的半胱天冬酶活性阻止细胞迁移,以保持组织的完整性。
Maintenance of tissue integrity during development and homeostasis requires the precise coordination of several cell-based processes, including cell death. In animals, the majority of such cell death occurs by apoptosis, a process mediated by caspase proteases. To elucidate the role of caspases in tissue integrity, we investigated the behavior of Drosophila epithelial cells that are severely compromised for caspase activity. We show that these cells acquire migratory and invasive capacities, either within 1–2 days following irradiation or spontaneously during development. Importantly, low levels of effector caspase activity, which are far below the threshold required to induce apoptosis, can potently inhibit this process, as well as a distinct, developmental paradigm of primordial germ cell migration. These findings may have implications for radiation therapy in cancer treatment. Furthermore, given the presence of caspases throughout metazoa, our results could imply that preventing unwanted cell migration constitutes an ancient non-apoptotic function of these proteases. In addition to regulating programmed cell death, caspases also have non-apoptotic roles. Here, the authors show that low level caspase activity prevents cell migration to maintain tissue integrity.
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