Wnt signaling stimulates transcriptional outcome of the hedgehog pathway by stabilizing GLI1 mRNA

Felicite K. Noubissi; Srikanta Goswami; Nicholas A. Sanek; Kazuyuki Kawakami; Toshinari Minamoto; Amy Moser; Yevgenya Grinblat; Vladimir S. Spiegelman

doi:10.1158/0008-5472.CAN-09-1500

Wnt signaling stimulates transcriptional outcome of the hedgehog pathway by stabilizing GLI1 mRNA

Felicite K. Noubissi, Srikanta Goswami, Nicholas A. Sanek, Kazuyuki Kawakami, Toshinari Minamoto, Amy Moser, Yevgenya Grinblat, Vladimir S. Spiegelman

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Abstract

Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. However, the mechanisms by which these two pathways interact are not well understood. Here, we identified a novel mechanism by which Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. Wnt/β-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which in turn binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 seems to be important to several functions of Wnt, including survival and proliferation of colorectal cancer cells.

Original language	English (US)
Pages (from-to)	8572-8578
Number of pages	7
Journal	Cancer Research
Volume	69
Issue number	22
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-1500
State	Published - Nov 15 2009
Externally published	Yes

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title = "Wnt signaling stimulates transcriptional outcome of the hedgehog pathway by stabilizing GLI1 mRNA",

abstract = "Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. However, the mechanisms by which these two pathways interact are not well understood. Here, we identified a novel mechanism by which Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. Wnt/β-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which in turn binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 seems to be important to several functions of Wnt, including survival and proliferation of colorectal cancer cells.",

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AU - Noubissi, Felicite K.

AU - Goswami, Srikanta

AU - Sanek, Nicholas A.

AU - Kawakami, Kazuyuki

AU - Minamoto, Toshinari

AU - Moser, Amy

AU - Grinblat, Yevgenya

AU - Spiegelman, Vladimir S.

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AB - Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. However, the mechanisms by which these two pathways interact are not well understood. Here, we identified a novel mechanism by which Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. Wnt/β-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which in turn binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 seems to be important to several functions of Wnt, including survival and proliferation of colorectal cancer cells.

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Wnt signaling stimulates transcriptional outcome of the hedgehog pathway by stabilizing GLI1 mRNA

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