癌症中的S100蛋白
S100 proteins in cancer.
作者信息
Bresnick Anne R, Weber David J, Zimmer Danna B
机构信息
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, Maryland 20102, USA.
出版信息
Nat Rev Cancer. 2015 Feb;15(2):96-109. doi: 10.1038/nrc3893.
In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca(2+) sensors and as extracellular factors. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.
在人类中，S100蛋白家族由21个成员组成，这些成员表现出高度的结构相似性，但功能上不可互换。该蛋白家族通过作为细胞内钙（2+）传感器和细胞外因子发挥作用来调节细胞反应。S100家族多个成员的表达失调是人类癌症的一个共同特征，每种癌症都显示出独特的S100蛋白谱或特征。新出现的体内证据表明，大多数S100蛋白的生物学特性复杂且多因素，并且这些蛋白积极参与肿瘤发生过程，如细胞增殖、转移、血管生成和免疫逃避。药物研发工作已确定了抑制多个S100家族成员的先导化合物，其中两种已鉴定的抑制剂已进入癌症患者的临床试验阶段。本综述重点介绍了关于S100家族成员在癌症诊断和治疗中的作用、S100信号传导对肿瘤生物学的贡献以及用于治疗癌症的S100抑制剂的发现和开发的新发现。
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