Role of CRD-BP in the growth of human basal cell carcinoma cells

Felicite K. Noubissi, Taewon Kim, Tisha N. Kawahara, William D. Aughenbaugh, Eric Berg, B. Jack Longley, Mohammad Athar, Vladimir S. Spiegelman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Although the number of new cases of basal cell carcinoma (BCC) has increased rapidly in the last few decades, the molecular basis of its pathogenesis is not completely understood. Activation of the Hedgehog (Hh) signaling pathway has been shown to be a key factor driving the development of BCC. The Wnt/β-catenin signaling pathway was also shown to be activated in BCCs and to perhaps modulate the activity of the Hh pathway. We have previously identified a mechanism by which Wnt signaling regulates the transcriptional outcome of the Hh signaling pathway. We demonstrated that coding region determinant-binding protein (CRD-BP), a direct target of the Wnt/β-catenin signaling, binds to GLI1 mRNA, stabilizes it, and consequently upregulates its levels (mRNA and protein) and activities. We hypothesized that Wnt-induced and CRD-BP-dependent regulation of GLI1 expression and activities is important for the development of BCC. In this study, we show that CRD-BP is overexpressed in BCC and that its expression positively correlates with the activation of both Wnt and Hh signaling pathways. We also describe the generation and characterization of a human BCC cell line. This cell line was utilized to demonstrate the importance of CRD-BP-dependent regulation of GLI1 expression and activities in the development of BCC.

Original languageEnglish (US)
Pages (from-to)1718-1724
Number of pages7
JournalJournal of Investigative Dermatology
Volume134
Issue number6
DOIs
StatePublished - Jun 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Noubissi, F. K., Kim, T., Kawahara, T. N., Aughenbaugh, W. D., Berg, E., Longley, B. J., Athar, M., & Spiegelman, V. S. (2014). Role of CRD-BP in the growth of human basal cell carcinoma cells. Journal of Investigative Dermatology, 134(6), 1718-1724. https://doi.org/10.1038/jid.2014.17