Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1.

Abstract

LIM and SH3 protein 1 (LASP-1), initially identified from a cDNA library of metastatic axillary lymph nodes of breast cancer patients, is a specific focal adhesion protein involved in numerous biological and pathological processes. The overexpression of LASP-1 has been described in several types of cancers, but the role of LASP-1 in colorectal cancer (CRC) is unknown. In a previous study, comparative proteomic analysis was performed and LASP-1 was identified as a CRC-associated protein in those patients with CRC. Using immunohistochemistry, we analysed LASP-1 protein expression in 126 clinicopathologically characterised CRC cases. Using gene transfection and RNA interference, we investigated the effects of LASP-1 overexpression and depletion on tumor cellular behavior in vitro and in vivo. Using 2-D DIGE, we analysed the effect of the presence and absence of LASP-1 gene on protein expression profiles of CRC cells. Overexpression of LASP-1 was found in metastatic CRC tissues (p=0.002), and its expression level was closely correlated with overall survival of patients with CRC (p=0.002). RNA interference-mediated silencing of the LASP-1 gene in SW620 CRC cells inhibited cell proliferation and migration significantly. However, gene transfection-mediated overexpression of LASP-1 in SW480 CRC cells resulted in aggressive phenotypes of cancer cells and promoted cancer growth and metastasis. Furthermore, both overexpression and silencing of the LASP-1 gene caused a very similar protein expression pattern in different CRC cell lines. The identified LASP-1-modulated proteins, including some key cellular molecules, were involved in various biological processes. The results show that LASP-1 might be a promising target in the treatment of patients with CRC with growth and metastasis of CRC.