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

      Gut
      Adaptor Proteins, Signal Transducing, genetics, physiology, Animals, Cell Movement, Cell Proliferation, Colorectal Neoplasms, metabolism, pathology, Cytoskeletal Proteins, Disease Progression, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, methods, Humans, LIM Domain Proteins, Mice, Mice, Nude, Neoplasm Metastasis, physiopathology, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Prognosis, RNA, Messenger, RNA, Neoplasm, Tumor Cells, Cultured

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          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.

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