Sion Amy M, Figg William D
Clinical Pharmacology Program, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Biol Ther. 2006 Aug;5(8):909-11. doi: 10.4161/cbt.5.8.3230. Epub 2006 Aug 26.
Angiogenesis is a critical process in the transition of tumors from a localized, primary site to a distant site of metastases. Hypoxic conditions within the tumor mass lead to the activation of signalling pathways which initiate tumor cell invasion, migration, adhesion and subsequent angiogenesis. Several key molecular players in hypoxia-induced tumor progression are well-described, e.g., hypoxia-inducible factor-1 (HIF-1) and angiopoietin-2; however, drug development aimed at suppressing individual members of this signalling cascade has proven to be challenging. The article by Erler et al. published in Nature (Vol. 440, April 2006) identifies lysyl oxidase (LOX) as an essential enzyme for hypoxia-induced metastases. This Journal Club reviews the findings presented by Erler and colleagues and briefly discusses the implications of LOX in cancer.
血管生成是肿瘤从局部原发部位转移至远处转移部位过程中的关键环节。肿瘤块内的缺氧状态会导致信号通路激活,进而引发肿瘤细胞的侵袭、迁移、黏附以及随后的血管生成。缺氧诱导的肿瘤进展中的几个关键分子参与者已得到充分描述,例如缺氧诱导因子-1(HIF-1)和血管生成素-2;然而,旨在抑制该信号级联中单个成员的药物研发已被证明具有挑战性。埃勒等人发表于《自然》(2006年4月,第440卷)的文章将赖氨酰氧化酶(LOX)确定为缺氧诱导转移所必需的一种酶。本期期刊俱乐部回顾了埃勒及其同事所展示的研究结果,并简要讨论了LOX在癌症中的意义。
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