LIM and SH3 Protein 1 (LASP1) is a member of a subfamily of LIM proteins, characterized by a LIM motif and a domain of Src homology region 3 (SH3). It is also a member of the nebulin family of actin-binding proteins . LASP1 was first identified in lymph nodes of breast cancer patients in 1995 . The gene encoding LASP1 is located on chromosome 17q11-21.3 and encodes a protein of 261 amino acids .
The structural analysis of LASP1 reveals a protein composed of:
The first nebulin repeat includes a nuclear export signal (NES; aa 71–77) . The LIM domain, nebulin repeats, and SH3 domain are highly conserved among vertebrates and invertebrates .
Originally identified as a structural cytoskeletal protein with scaffolding function, recent data suggest additional roles for LASP1 in cell signaling and gene expression, especially in tumor cells . These novel functions are primarily regulated by the site-specific phosphorylation of LASP1 .
LASP1 is involved in various cellular processes such as proliferation, migration, tumorigenesis, and chemoresistance . It plays a significant role in the PI3K/AKT signaling pathway, which is crucial for cell growth and survival . LASP1 is also implicated in the regulation of chemokine receptor signaling, particularly CXCR4 .
In addition to its cytoskeletal functions, LASP1 has roles in the nucleus, where it is involved in epigenetics and transcriptional regulation . It modulates oncogenic mRNA translation and interacts with various cellular proteins to orchestrate primary tumor progression and metastasis .
LASP1 is upregulated in several types of human cancer and is implicated in cancer progression . High LASP1 expression is associated with poor overall survival in glioblastoma (GBM) patients . LASP1 knockdown has been shown to suppress cell proliferation and enhance chemosensitivity to temozolomide in GBM . This makes LASP1 a promising target for therapeutic strategies in cancer treatment .