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ADAM28: Another ambivalent protease in cancer.
Cancer Letters ( IF 9.7 ) Pub Date : 2020-08-28 , DOI: 10.1016/j.canlet.2020.08.031
Céline Hubeau 1 , Natacha Rocks 2 , Didier Cataldo 3
Affiliation  

Emergence of novel therapeutic options in a perspective of personalized therapy of cancer relies on the discovery of precise molecular mechanisms involved in the switch from a localized tumor to invasive metastasis spread. Pro-tumor functions have been mostly ascribed to proteolytic enzymes from the metalloproteinase family including A Disintegrin And Metalloproteinases (ADAMs). Particularly, when expressed by cancer cells, ADAM28 protease supports cancer cell proliferation, survival and migration as well as metastatic progression. In sharp contrast, ADAM28 derived from the tumor microenvironment has shown to exert strong protective effects against deleterious metastasis dissemination. Indeed, depletion of host-derived ADAM28 (ADAM28 KO mice) accelerates colonization lung tissues, increases tumor foci implantation, and impairs T cell immune response.

In this review, we outline specific ADAM28 functions when specifically expressed by carcinoma cells or by tumor microenvironment. Finally, we discuss about future research strategies that could be pursued to highlight new functions of this protease in cancer.



中文翻译:

ADAM28:癌症中另一种矛盾的蛋白酶。

从癌症的个性化治疗的角度来看,新的治疗选择的出现依赖于精确分子机制的发现,该分子机制涉及从局部肿瘤向侵袭性转移扩散的转变。促肿瘤功能主要归因于来自金属蛋白酶家族的蛋白水解酶,包括解粘蛋白和金属蛋白酶(ADAM)。特别地,当由癌细胞表达时,ADAM28蛋白酶支持癌细胞的增殖,存活和迁移以及转移进展。与之形成鲜明对比的是,源自肿瘤微环境的ADAM28已显示出强大的保护作用,可防止有害的转移扩散。实际上,宿主来源的ADAM28(ADAM28 KO小鼠)的耗竭会加速肺组织的定植,增加肿瘤灶的植入,

在这篇综述中,我们概述了由癌细胞或肿瘤微环境特异性表达的特定ADAM28功能。最后,我们讨论了未来的研究策略,可以用来突出这种蛋白酶在癌症中的新功能。

更新日期:2020-09-07
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