Interplay between SOX9, β-catenin and PPARγ activation in colorectal cancer

Anna Panza, Valerio Pazienza, Maria Ripoli, Giorgia Benegiamo, Annamaria Gentile, Maria Rosaria Valvano, Bartolomeo Augello, Giuseppe Merla, Clelia Prattichizzo, Francesca Tavano, Elena Ranieri, Pierluigi di Sebastiano, Manlio Vinciguerra, Angelo Andriulli, Gianluigi Mazzoccoli, Ada Piepoli

Research output: Contribution to journalArticle

Abstract

Colorectal carcinogenesis relies on loss of homeostasic mechanisms regulating cell proliferation, differentiation and survival. These cell processes have been reported to be influenced independently by transcription factors activated downstream of the Wnt pathway, such as SOX9 and β-catenin, and by the nuclear receptor PPARγ. The purpose of this study was to explore the expression levels and functional link between SOX9, β-catenin and PPARγ in the pathogenesis of colorectal cancer (CRC). We evaluated SOX9, β-catenin and PPARγ expression levels on human CRC specimens by qPCR and immunoblot detection. We tested the hypothesis that PPARγ activation might affect SOX9 and β-catenin expression using four colon cancer cell lines (CaCo2, SW480, HCT116, and HT29 cells). In CRC tissues SOX9 resulted up-regulated at both mRNA and protein levels when compared to matched normal mucosa, β-catenin resulted up-regulated at protein level. s, while PPARG mRNA and PPARγ protein levels were down-regulated. A significant relationship was observed between high PPARG and SOX9 expression levels in the tumor tissue and female gender (p. =. 0.005 and p. =. 0.04, respectively), and between high SOX9 expression in the tumor tissue and age (p. =. 0.04) and microsatellite instability (MSI), in particular with MSI-H (p. =. 0.0002). Moreover, treatment with the synthetic PPARγ ligand rosiglitazone induced different changes of SOX9 and β-catenin expression and subcellular localization in the colon cancer cell lines examined. In conclusion, SOX9, β-catenin and PPARγ expression levels are deregulated in the CRC tissue, and in colon cancer cell lines ligand-dependent PPARγ activation unevenly influences SOX9 and β-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis.

Original languageEnglish
Pages (from-to)1853-1865
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number8
DOIs
Publication statusPublished - Aug 2013

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Keywords

  • β-catenin
  • Colon cancer cell lines
  • Colorectal cancer
  • PPARγ
  • SOX9

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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