TY - JOUR
T1 - Role of CRD-BP in the growth of human basal cell carcinoma cells
AU - Noubissi, Felicite K.
AU - Kim, Taewon
AU - Kawahara, Tisha N.
AU - Aughenbaugh, William D.
AU - Berg, Eric
AU - Longley, B. Jack
AU - Athar, Mohammad
AU - Spiegelman, Vladimir S.
N1 - Funding Information:
We thank the Department of Dermatology at UW Madison for providing logistics during the collection of the BCC samples, I Siddiqui for helping with the generation of tumors in nude mice, and K Spiegelman for editing the manuscript. This work was supported by a Dermatology Foundation Career Development Award (to FKN) and NIH grants CA153102 (to FKN), CA121851, and AR063361 (to VSS).
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2014.17
DO - 10.1038/jid.2014.17
M3 - Article
C2 - 24468749
AN - SCOPUS:84900866516
SN - 0022-202X
VL - 134
SP - 1718
EP - 1724
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -