Department of Molecular Chemoprevention and Therapeutics, University of Minnesota, Austin, MN 55912, USA.
Cancer Metastasis Rev. 2012 Jun;31(1-2):163-72. doi: 10.1007/s10555-011-9338-4.
The fatality of cancer is mainly bestowed to the property of otherwise benign tumor cells to become malignant and invade surrounding tissues by circumventing normal tissue barriers through a process called metastasis. S100A4 which is a member of the S100 family of calcium-binding proteins has been shown to be able to activate and integrate pathways both intracellular and extracellular to generate a phenotypic response characteristic of cancer metastasis. A large number of studies have shown an increased expression level of S100A4 in various types of cancers. However, its implications in cancer metastasis in terms of whether an increased expression of S100A4 is a causal factor for metastasis or just another after effect of several other physiological and molecular changes in the body resulting from metastasis are not clear. Here we describe the emerging preclinical and clinical evidences implicating S100A4 protein, in both its forms (intracellular and extracellular) in the process of tumorigenesis and metastasis in humans. Based on studies utilizing S100A4 as a metastasis biomarker and molecular target for therapies such as gene therapy, we suggest that S100A4 has emerged as a promising molecule to be tested for anticancer drugs. This review provides an insight in the (1) molecular mechanisms through which S100A4 drives the tumorigenesis and metastasis and (2) developments made in the direction of evaluating S100A4 as a cancer biomarker and drug target.
癌症的致命性主要归因于良性肿瘤细胞的属性，即通过绕过正常组织屏障的过程（称为转移）而恶性化并侵犯周围组织。S100A4 是钙结合蛋白 S100 家族的成员之一，已被证明能够激活和整合细胞内和细胞外的途径，产生癌症转移的表型反应特征。大量研究表明，S100A4 在各种类型的癌症中的表达水平增加。然而，其在癌症转移中的意义，即 S100A4 的表达增加是转移的因果因素，还是转移导致的身体内其他几个生理和分子变化的另一个后效，尚不清楚。在这里，我们描述了涉及 S100A4 蛋白（其细胞内和细胞外形式）在人类肿瘤发生和转移过程中的新兴临床前和临床证据。基于利用 S100A4 作为转移生物标志物和基因治疗等治疗方法的分子靶标的研究，我们认为 S100A4 已成为一种有前途的分子，可以用于测试抗癌药物。这篇综述提供了对以下方面的深入了解：(1) S100A4 驱动肿瘤发生和转移的分子机制，以及 (2) 评估 S100A4 作为癌症生物标志物和药物靶标的进展。
