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Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1
  1. Liang Zhao1,2,
  2. Hui Wang3,
  3. Chao Liu2,
  4. Yawei Liu4,
  5. Xiaoyan Wang2,
  6. Shuang Wang2,
  7. Xuegang Sun5,
  8. Jianming Li2,
  9. Yongjian Deng2,
  10. Yong Jiang4,
  11. Yanqing Ding1,2
  1. 1Department of Pathology, Nanfang Hospital, Southern Medical University, China
  2. 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, China
  3. 3Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, China
  4. 4Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, China
  5. 5School of Traditional Chinese Medicine, Southern Medical University, China
  1. Correspondence to Yanqing Ding, Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China;dyqsmu{at}sina.com

Abstract

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
  • proteomics
  • colorectal carcinoma
  • colorectal neogenesis

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Footnotes

  • 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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