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Abstract
The Hedgehog pathway is critical for the development of diverse organs. Misactivation of the Hedgehog pathway can cause developmental abnormalities and cancers, including medulloblastoma, the most common pediatric brain tumor, and basal cell carcinoma, the most common cancer in the United States. Here, we review how basic, translational, and clinical studies of the Hedgehog pathway have helped reveal how cells communicate, how intercellular communication controls development, how signaling goes awry to cause cancer, and how to use targeted molecular agents to treat both inherited and sporadic cancers.
Authors
David R. Raleigh, Jeremy F. Reiter
Figure 3
A model of the Hedgehog transcriptional program in cancer.
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Misactivation of the Hedgehog pathway in cancer through upstream mutations, gene amplification, atypical protein kinase C (aPKC) signaling, or epigenetic misregulation of the SWI/SNF chromatin remodeling complex or BET bromodomain proteins culminates in activation of GLI transcription factors. GLI transcription factors induce the expression of N-MYC , CDK6 , CCND1 , and CCND2 to promote cancer cell proliferation and tumor growth. Parallel activation of Cdk5 and PI3K/mTOR signaling may facilitate evasion of immune elimination and resistance to SMO antagonists, respectively.
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ISSN: 0021-9738 (print), 1558-8238 (online)