Abstract
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.
Highlights
In 1995 Tomasetto et al identified four genes in a cDNA library of metastatic axillary lymph nodes from breast cancer, one of them was termed MLN50 [1]
As LIM and SH3 domain protein 1 (LASP1) is the first protein that combines both, LIM and SRC homology region 3 (SH3) domains, and as it contains two nebulin-like repeats, it defines a new LIM protein subfamily of the nebulin group [2,3]. This unique domain composition renders LASP1 to be a potentially extremely versatile protein and may shed light on its diverse cellular functions: The conserved zinc-binding modules are structurally related to the DNAbinding zinc-finger domains of nuclear hormone receptors and likely form functionally independent folding-units, suggesting that LIM domains may bind to DNA [4]
A co-overexpression of LASP1 with the ERBB2 (Her2/neu) oncogene was reported for human breast cancer tissues, as both genes are in close vicinity on the 17q11-21 region
Summary
In 1995 Tomasetto et al identified four genes in a cDNA library of metastatic axillary lymph nodes from breast cancer, one of them was termed MLN50 [1]. The transcribed 4.0kb mRNA encodes a protein of 261 amino acids (Fig.1) This protein contains an N-terminal LIM domain, which is composed of two sequential zinc-binding modules with a typical LIM motif, followed by tandem 35-residue nebulin-like repeats named R1 and R2, and by a C-terminal SRC homology region 3 (SH3) domain. As LASP1 is the first protein that combines both, LIM and SH3 domains, and as it contains two nebulin-like repeats, it defines a new LIM protein subfamily of the nebulin group [2,3]. Numerous binding partners of LASP1 have www.impactjournals.com/oncotarget
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