Role of CRD-BP in the growth of human basal cell carcinoma cells.
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.
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. Electronic address: fnoubiss@umn.edu.
Felicite K
FK
Noubissi
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Molecular and Environmental Toxicology Center Graduate Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
TaeWon
T
Kim
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Tisha N
TN
Kawahara
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
William D
WD
Aughenbaugh
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Eric
E
Berg
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
B Jack
BJ
Longley
Department of Dermatology, University of Alabama, Birmingham, Alabama, USA.
Mohammad
M
Athar
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Molecular and Environmental Toxicology Center Graduate Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Vladimir S
VS
Spiegelman
D000818:Animals; D017209:Apoptosis; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D000071676:Zinc Finger Protein GLI1
C519161:CRD-BP protein, mouse; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C406144:IGF2BP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C509186:TERT protein, human; D019098:Telomerase