title: Overexpression of galectin-3 enhances migration of colon cancer cells related to activation of the K-Ras-Raf-Erk1/2 pathway.
abstract: 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.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Keng-Liang
authors.initials: KL
authors.lastname: Wu
authors.forename: Eng-Yen
authors.initials: EY
authors.lastname: Huang
authors.forename: En-Wei
authors.initials: EW
authors.lastname: Jhu
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Huang
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Su
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Chuang
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D037502:Galectin 3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D048490:raf Kinases / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
chemical_list: D037502:Galectin 3; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D048490:raf Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins