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Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
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2010 (English)In: ONCOGENE, ISSN 0950-9232, Vol. 29, no 4, 516-526 p.Article in journal (Refereed) Published
Abstract [en]

The role of peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-beta expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-beta 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-beta 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-beta 1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-beta 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-beta 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-beta seems to have a more important role in poorly metastatic cells than in highly metastatic ones.

Place, publisher, year, edition, pages
2010. Vol. 29, no 4, 516-526 p.
Keyword [en]
peroxisome proliferator-activated receptor, colon neoplasm, pathogenesis, RNA interference, differentiation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-54059DOI: 10.1038/onc.2009.370ISI: 000274084600005OAI: oai:DiVA.org:liu-54059DiVA: diva2:298314
Available from: 2010-02-22 Created: 2010-02-22 Last updated: 2013-10-22

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Yang, LieOlsson, BirgitPfeifer, DaniellaJönsson, J-IFredriksson, Bengt-ArneSun, Xiao-Feng

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Yang, LieOlsson, BirgitPfeifer, DaniellaJönsson, J-IFredriksson, Bengt-ArneSun, Xiao-Feng
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Department of Clinical and Experimental MedicineFaculty of Health SciencesOncologyDepartment of Oncology UHL
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