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癌症:创伤愈合的阴暗面。

Cancer: the dark side of wound healing.

机构信息

Institute of Medical Biology, Agency for Science Technology & Research (A*STAR), Singapore City, Singapore.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.

出版信息

FEBS J. 2018 Dec;285(24):4516-4534. doi: 10.1111/febs.14586. Epub 2018 Jun 25.

Abstract

Complex multicellular organisms have evolved sophisticated mechanisms to rapidly resolve epithelial injuries. Epithelial integrity is critical to maintaining internal homeostasis. An epithelial breach represents the potential for pathogen ingress and fluid loss, both of which may have severe consequences if not limited. The mammalian wound healing response involves a finely tuned, self-limiting series of cellular and molecular events orchestrated by the transient activation of specific signalling pathways. Accurate regulation of these events is essential; failure to initiate key steps at the right time delays healing and leads to chronic wounds, while aberrant initiation of wound healing processes may produce cell behaviours that promote cancer progression. In this review, we discuss how wound healing pathways co-opted in cancer lose their stringent regulation and become compromised in their reversibility. We hypothesize on how the commandeering of wound healing 'master regulators' is involved in this process, and also highlight the implications of these findings in the treatment of both chronic wounds and cancer.

摘要

复杂的多细胞生物已经进化出了复杂的机制,可以迅速修复上皮损伤。上皮完整性对于维持内部平衡至关重要。上皮破裂代表病原体入侵和液体流失的可能性,如果不加以限制,这两者都可能产生严重的后果。哺乳动物的伤口愈合反应涉及一系列精细调节、自我限制的细胞和分子事件,这些事件由特定信号通路的短暂激活来协调。这些事件的准确调节至关重要;如果不能在正确的时间启动关键步骤,就会延迟愈合,导致慢性伤口,而伤口愈合过程的异常启动可能会产生促进癌症进展的细胞行为。在这篇综述中,我们讨论了在癌症中被劫持的伤口愈合途径如何失去其严格的调控,并在其可逆性方面受到损害。我们推测了伤口愈合“主调控因子”的接管如何参与这一过程,并强调了这些发现对慢性伤口和癌症治疗的意义。

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