Overexpression of galectin-3 enhances migration of colon cancer cells related to activation of the K-Ras-Raf-Erk1/2 pathway

Keng Liang Wu, Eng Yen Huang, En Wei Jhu, Ya Hui Huang, Wen Hong Su, Pei Chin Chuang, Kuender D. Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

56 Scopus citations

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.

Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalJournal of Gastroenterology
Volume48
Issue number3
DOIs
StatePublished - 03 2013

Keywords

  • Cell migration
  • Colorectal carcinoma
  • Erk1/2
  • Galectin-3
  • K-Ras
  • P38

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