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Knockdown of peroxisome proliferator-activated receptor-β induces less differentiation and enhances cell–fibronectin adhesion of colon cancer cells

Oncogene volume 29, pages 516–526 (2010)Cite this article

Abstract

The role of peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-β expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-β knockdown resulted in more malignant morphological changes, bigger colony sizes and lower carcinoembryonic antigen (CEA) secretion, and enhanced the cell–fibronectin adhesion, cell invasion and migration were unaffected. These effects were stronger in poorly metastatic cell lines compared with highly metastatic ones. Simultaneously, PPAR-β knockdown decreased the mRNAs encoding adipocyte differentiation-related protein and liver fatty acid binding protein, and increased the mRNA of ILK, whereas the mRNAs encoding integrin-β1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-β expression was stronger in rectal cancers with better differentiation than in those with poor differentiation, and was stronger in early-stage tumors than in advanced ones. Together, these findings consistently indicate that PPAR-β may facilitate differentiation and inhibit the cell–fibronectin adhesion of colon cancer, having a role as an inhibitor in the carcinogenesis and progression of colorectal cancer. Interestingly, PPAR-β seems to have a more important role in poorly metastatic cells than in highly metastatic ones.

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Acknowledgements

We thank Petter Hammar (Linköping University, Sweden) for his help in lentivirus construction, and thank Prof IJ Fidler (Anderson Cancer Center, Houston, TX) for offering KM12 cell lines. This study was financially supported by grants from the Swedish Cancer Foundation, Swedish Research Council and the Health Research Council in the South-East of Sweden, the Natural Science Foundation of China (Grant No. 30801332) and the National Science Foundation for post-doctoral Scientists of China (Grant No. 20070421149).

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Authors and Affiliations

  1. Division of Oncology, Department of Clinical and Experiment Medicine, Linköping University, Linköping, Sweden

    L Yang, B Olsson, D Pfeifer & X -F Sun

  2. Division of Experimental Hematology, Department of Clinical and Experiment Medicine, Linköping University, Linköping, Sweden

    J -I Jönsson

  3. Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan Province, PR China

    L Yang, Z -G Zhou & X Jiang

  4. Division of Experimental Pathology, Department of Clinical and Experiment Medicine, Linköping University, Linköping, Sweden

    B -A Fredriksson

  5. Division of Biomedicine, University of Skövde, Skövde, Sweden

    H Zhang

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Correspondence to X -F Sun.

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Yang, L., Olsson, B., Pfeifer, D. et al. Knockdown of peroxisome proliferator-activated receptor-β induces less differentiation and enhances cell–fibronectin adhesion of colon cancer cells. Oncogene 29, 516–526 (2010). https://doi.org/10.1038/onc.2009.370

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