Orth Martin F, Cazes Alex, Butt Elke, Grunewald Thomas G P
Institute for Clinical Biochemistry and Pathobiochemistry, University Clinic of Würzburg, Grombühlstrasse, Würzburg, Germany.
Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Thalkirchner Strasse, Munich, Germany.
Oncotarget. 2015 Jan 1;6(1):26-42. doi: 10.18632/oncotarget.3083.
The gene encoding the LIM and SH3 domain protein (LASP1) was cloned two decades ago from a cDNA library of breast cancer metastases. As the first protein of a class comprising one N-terminal LIM and one C-terminal SH3 domain, LASP1 founded a new LIM-protein subfamily of the nebulin group. Since its discovery LASP1 proved to be an extremely versatile protein because of its exceptional structure allowing interaction with various binding partners, its ubiquitous expression in normal tissues, albeit with distinct expression patterns, and its ability to transmit signals from the cytoplasm into the nucleus. As a result, LASP1 plays key roles in cell structure, physiological processes, and cell signaling. Furthermore, LASP1 overexpression contributes to cancer aggressiveness hinting to a potential value of LASP1 as a cancer biomarker. In this review we summarize published data on structure, regulation, function, and expression pattern of LASP1, with a focus on its role in human cancer and as a biomarker protein. In addition, we provide a comprehensive transcriptome analysis of published microarrays (n=2,780) that illustrates the expression profile of LASP1 in normal tissues and its overexpression in a broad range of human cancer entities.
编码LIM和SH3结构域蛋白（LASP1）的基因是20年前从乳腺癌转移灶的cDNA文库中克隆出来的。作为一类包含一个N端LIM和一个C端SH3结构域的首个蛋白，LASP1开创了肌动蛋白结合蛋白家族的一个新的LIM蛋白亚家族。自发现以来，LASP1因其特殊结构允许与各种结合伴侣相互作用、在正常组织中普遍表达（尽管表达模式不同）以及将信号从细胞质传递到细胞核的能力，被证明是一种极其多功能的蛋白。因此，LASP1在细胞结构、生理过程和细胞信号传导中发挥关键作用。此外，LASP1的过表达促进癌症侵袭性，这暗示了LASP1作为癌症生物标志物的潜在价值。在本综述中，我们总结了已发表的关于LASP1的结构、调控、功能和表达模式的数据，重点关注其在人类癌症中的作用以及作为生物标志物蛋白的作用。此外，我们对已发表的微阵列（n = 2780）进行了全面的转录组分析，展示了LASP1在正常组织中的表达谱及其在多种人类癌症实体中的过表达情况。
