The LIM and SH3 domain protein (lasp) family, the smallest proteins in the nebulin superfamily, consists of vertebrate lasp-1 expressed in various non-muscle tissues, vertebrate lasp-2 expressed in the brain and cardiac muscle, and invertebrate lasp whose functions have been analyzed in Ascidiacea and Insecta. Gene evolution of the lasp family proteins was investigated by multiple alignments, comparison of gene structure, and synteny analyses in eukaryotes in which mRNA expression was confirmed. All invertebrates analyzed in this study belonging to the clade Filasterea, with the exception of Placozoa, have at least one lasp gene. The minimal actin-binding region (LIM domain and first nebulin repeat) and SH3 domain detected in vertebrate lasp-2 were found to be conserved among the lasp family proteins, and we showed that nematode lasp has actin-binding activity. The linker sequences vary among invertebrate lasp proteins, implying that the lasp family proteins have universal and diverse functions. Gene structures and syntenic analyses suggest that a gene fragment encoding two nebulin repeats and a linker emerged in Filasterea or Holozoa, and the first lasp gene was generated following combination of three gene fragments encoding the LIM domain, two nebulin repeats with a linker, and the SH3 domain.

The LIM and SH3 protein-1 (LASP-1) is a multi-domain protein that is involved in several malignant cancers. The role of LASP-1 in malignant phenotypes including high invasive properties and unrestricted cell proliferation, remain to be elucidated. The present study reported the association of LASP-1 expression with bladder cancer malignancy and its role in cancer cell invasion and proliferation. The immunohistochemical analysis of the expression status of LASP-1 in radical cystectomy specimens from invasive bladder cancer patients revealed that the LASP-1-positive patients demonstrated a decreased survival rate compared with the LASP-1-negative patients. The expression level of LASP-1 was increased in invasive bladder cancer cell lines compared with the non-invasive bladder cancer cell lines. Invasive cancer cells form invadopodia, the filamentous actin-based membrane protrusions that are essential in cancer cell invasion. Knockdown of LASP-1 reduced the ability to form invadopodia, resulting in decreased invasive capacity of the LASP-1 knockdown cells. In addition, knockdown of LASP-1 reduced cell proliferation. These results suggest that LASP-1 is important in invadopodia formation and cell proliferation of bladder cancer cells, promoting the malignant properties and resulting in poor-prognosis.