Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1.
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.
Zhao
Liang
L
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China.
Wang
Hui
H
Liu
Chao
C
Liu
Yawei
Y
Wang
Xiaoyan
X
Wang
Shuang
S
Sun
Xuegang
X
Li
Jianming
J
Deng
Yongjian
Y
Jiang
Yong
Y
Ding
Yanqing
Y
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology; D009368:Neoplasm Transplantation; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm