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破坏基质金属蛋白酶功能:对癌症发展的影响

RECKing MMP function: implications for cancer development.

作者信息

Rhee Jin-Sae, Coussens Lisa M

机构信息

Medical Scientist Training Program and Cancer Research Institute, University of California, San Francisco, 2340 Sutter St, 94143, USA.

出版信息

Trends Cell Biol. 2002 May;12(5):209-11. doi: 10.1016/s0962-8924(02)02280-8.

Abstract

Cancer is a multistage process requiring progressive genetic and epigenetic changes in neoplastic and responding stromal cells. Many alterations that occur during the process of malignant progression are regulated by the matrix metalloproteinase (MMP) family of extracellular proteases and their endogenous inhibitors. Recent work has identified a new cell-surface inhibitor of MMPs - RECK. RECK regulates MMP-induced pericellular signaling cascades during embryogenesis and tumorigenesis. Homozygous loss of RECK results in embryonic lethality and attenuated tumor development in adults - thus providing further support for an efficacious role for protease inhibitors as anticancer therapeutics.

摘要

癌症是一个多阶段过程,需要肿瘤细胞和反应性基质细胞发生渐进性的基因和表观遗传变化。恶性进展过程中发生的许多改变都受细胞外蛋白酶基质金属蛋白酶(MMP)家族及其内源性抑制剂的调控。最近的研究发现了一种新的MMP细胞表面抑制剂——RECK。RECK在胚胎发育和肿瘤发生过程中调节MMP诱导的细胞周围信号级联反应。RECK的纯合缺失导致胚胎致死,并使成年个体的肿瘤发展减弱——从而为蛋白酶抑制剂作为抗癌治疗药物的有效作用提供了进一步支持。

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