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

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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.

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Acknowledgments

The study was supported by a Grant, CMRPG880621, CMRPG880622, from Chang Gung Memorial Hospital, Taiwan, and by Grant, NSC 100-2325-B-182A and 100-2325-B-182A-001 from the National Science Council, Taiwan, ROC. We thank Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital, Tissue Bank (CLRPG 870463) for providing the study materials.

Conflict of interest

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Authors and Affiliations

  1. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    Keng-Liang Wu

  2. Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    Eng-Yen Huang

  3. Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    En-Wei Jhu, Ya-Hui Huang, Wen-Hong Su & Pei-Chin Chuang

  4. Department of Medical Research, Show Chwan Memorial Hospital, Chang Bing, 6 Lu-Kung Road, Lu-gang District, Changhua, 505, Taiwan

    Kuender D. Yang

  5. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

    Keng-Liang Wu, Eng-Yen Huang & Kuender D. Yang

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  1. Keng-Liang Wu
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Correspondence to Kuender D. Yang.

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Wu, KL., Huang, EY., Jhu, EW. et al. Overexpression of galectin-3 enhances migration of colon cancer cells related to activation of the K-Ras–Raf–Erk1/2 pathway. J Gastroenterol 48, 350–359 (2013). https://doi.org/10.1007/s00535-012-0663-3

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  • DOI: https://doi.org/10.1007/s00535-012-0663-3

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