Document Detail


Overexpression of galectin-3 enhances migration of colon cancer cells related to activation of the K-Ras-Raf-Erk1/2 pathway.
MedLine Citation:
PMID:  23015305     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Galectin-3 has been independently correlated with malignant behavior in human colon cancer. The involvement of galectin-3 in the invasiveness of colon cancer cells remains to be determined. We investigated whether galectin-3 was involved in the colon cancer cell migration mediated by certain kinase pathways. METHODS: We studied 2 colon cancer cell lines (DLD-1 and Caco2) and clinical samples. Immunostaining and Western blotting were used to analyze the expression of galectin-3 in vitro and in the clinical samples. Short hairpin RNA and overexpression of galectin-3 were used to study loss- and gain-of-function in a wound-healing assay and a Transwell migration assay, and Western blotting was used to study the Ras-Raf signaling pathway. RESULTS: Galectin-3 was expressed at lower levels in DLD-1 than in Caco2 cells. The lower galectin-3 level in DLD-1 cells was associated with decreased cell migration, in comparison with that of Caco2 cells. Overexpression of galectin-3 increased the migration rate of DLD-1, while knockdown of galectin-3 decreased the migration. Overexpression of galectin-3 was correlated with increased lamellipodia formation and distal lung localization in a mouse model. The galectin-3 enhancement of DLD-1 cell migration was mediated by K-Ras, Raf and Erk1/2 pathway activation, but not the H-Ras, p38, or JNK activation. CONCLUSIONS: Galectin-3 plays an important role in regulating colon cancer cell migration and potential distal localization. The galectin-3 enhancement of cell migration is mediated through the K-Ras-Raf-Erk1/2 pathway. Specific targeting of the K-Ras-Raf-Erk1/2 pathway may be useful for treating colon cancers associated with increased galectin-3 expression.
Authors:
Keng-Liang Wu; Eng-Yen Huang; En-Wei Jhu; Ya-Hui Huang; Wen-Hong Su; Pei-Chin Chuang; Kuender D Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-27
Journal Detail:
Title:  Journal of gastroenterology     Volume:  -     ISSN:  1435-5922     ISO Abbreviation:  J. Gastroenterol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430794     Medline TA:  J Gastroenterol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
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