文章：

S100蛋白在癌症中的作用

S100 proteins in cancer

原文发布日期：2015-01-23

DOI: 10.1038/nrc3893

类型: Review Article

开放获取: 否

要点：

1. The S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable.
2. S100 family members function as intracellular Ca²⁺ sensors and extracellular factors.
3. Chromosomal alterations, mutations and/or translocations in S100 genes are rare in human cancers. Nonetheless, dysregulation of multiple S100 proteins is a common occurrence in individual human cancers and most often involves upregulation.
4. Each human cancer exhibits a distinctive S100 protein profile that can be both stage-specific and subtype-specific, as well as facilitate diagnosis, prognosis and/or drug response.
5. The modulation of S100 expression is a common downstream event in S100 signalling cascades, resulting in feedback loops that can sustain and exacerbate tumour progression.
6. The most common strategies for inhibiting S100 proteins exploit small molecules that block the hydrophobic cleft required for S100 proteins to interact with targets and elicit biological effects.
7. Inhibitors of two family members, S100B and S100A9, are in clinical trials for melanoma and prostate cancer, respectively.

要点翻译：

1. S100蛋白家族由21个结构高度相似但功能不可互换的成员组成。
2. S100家族成员兼具细胞内钙离子传感器和细胞外因子的功能。
3. 在人类癌症中，S100基因的染色体改变、突变和/或易位较为罕见。然而，多种S100蛋白的失调在个体癌症中普遍存在，且通常表现为表达上调。
4. 每种人类癌症都呈现独特的S100蛋白表达谱，这种表达谱既具有阶段特异性又具有亚型特异性，同时有助于诊断、预后判断和/或药物反应评估。
5. S100表达的调控是其信号传导通路中常见的下游事件，由此形成的反馈环路可维持并加剧肿瘤进展。
6. 目前抑制S100蛋白最常用的策略是利用小分子阻断S100蛋白与靶标相互作用并引发生物学效应所需的疏水裂隙。
7. 针对S100B和S100A9这两个家族成员的抑制剂已分别进入黑色素瘤和前列腺癌的临床试验阶段。

英文摘要：

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 Ca2+ 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.

摘要翻译： 

在人类中，S100蛋白家族由21个成员组成，它们具有高度的结构相似性，但在功能上不可互换。该家族蛋白通过作为细胞内Ca²⁺传感器和细胞外因子来调节细胞反应。多种S100家族成员表达失调是人类癌症的共同特征，每种癌症都显示出独特的S100蛋白谱或特征。新兴体内证据表明，大多数S100蛋白的生物学作用复杂且多因素，这些蛋白积极参与肿瘤发生过程，如细胞增殖、转移、血管生成和免疫逃逸。药物研发工作已发现抑制多个S100家族成员的先导化合物，其中两种抑制剂已进入癌症患者临床试验。本综述重点介绍S100家族成员在癌症诊断和治疗中的新发现、S100信号在肿瘤生物学中的作用，以及用于治疗癌症的S100抑制剂的发现和开发。

原文链接：

S100 proteins in cancer