Background 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.
Methods 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.
Results 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.
Conclusions The results show that LASP-1 might be a promising target in the treatment of patients with CRC with growth and metastasis of CRC.
- Colorectal cancer
- LIM and SH3 protein 1
- tumour metastasis
- poor prognosis
- colorectal carcinoma
- colorectal neogenesis
- Revised 8 March 2010
- Accepted 12 March 2010
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Funding This work was supported by a grant from the Key Science and Technology Research Program of Guangdong Province (no 2003A308401), National Basic Research Program of China (973 Program, no 2010CB529403), National Natural Science Foundation of China (no 30670967, 30770977, 30670968, 30971361 and 30901792), Natural Science Foundation of Guangdong Province (no 5200512) and the Foundation of President of School of Basic Medical Sciences of Southern Medical University (no JC0802).
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the the ethics committee of Southern Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.
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