Sonic hedgehog signaling in basal cell nevus syndrome

Mohammad Athar, Changzhao Li, Arianna L. Kim, Vladimir Spiegelman, David R. Bickers

Research output: Contribution to journalReview article

58 Citations (Scopus)

Abstract

The hedgehog (Hh) signaling pathway is considered to be a major signal transduction pathway during embryonic development, but it usually shuts down after birth. Aberrant Sonic hedgehog (Shh) activation during adulthood leads to neoplastic growth. Basal cell carcinoma (BCC) of the skin is driven by this pathway. Here, we summarize information related to the pathogenesis of this neoplasm, discuss pathways that crosstalk with Shh signaling, and the importance of the primary cilium in this neoplastic process. The identification of the basic/translational components of Shh signaling has led to the discovery of potential mechanism-driven druggable targets and subsequent clinical trials have confirmed their remarkable efficacy in treating BCCs, particularly in patients with nevoid BCC syndrome (NBCCS), an autosomal dominant disorder in which patients inherit a germline mutation in the tumor-suppressor gene Patched (Ptch). Patients with NBCCS develop dozens to hundreds of BCCs due to derepression of the downstream G-protein-coupled receptor Smoothened (SMO). Ptch mutations permit transposition of SMO to the primary cilium followed by enhanced expression of transcription factors Glis that drive cell proliferation and tumor growth. Clinical trials with the SMO inhibitor, vismodegib, showed remarkable efficacy in patients with NBCCS, which finally led to its FDA approval in 2012.

Original languageEnglish (US)
Pages (from-to)4967-4975
Number of pages9
JournalCancer Research
Volume74
Issue number18
DOIs
StatePublished - Aug 29 2014

Fingerprint

Basal Cell Nevus Syndrome
Cilia
HhAntag691
Clinical Trials
Neoplastic Processes
Germ-Line Mutation
Basal Cell Carcinoma
Growth
G-Protein-Coupled Receptors
Tumor Suppressor Genes
Embryonic Development
Signal Transduction
Neoplasms
Transcription Factors
Cell Proliferation
Parturition
Skin
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Athar, Mohammad ; Li, Changzhao ; Kim, Arianna L. ; Spiegelman, Vladimir ; Bickers, David R. / Sonic hedgehog signaling in basal cell nevus syndrome. In: Cancer Research. 2014 ; Vol. 74, No. 18. pp. 4967-4975.
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Sonic hedgehog signaling in basal cell nevus syndrome. / Athar, Mohammad; Li, Changzhao; Kim, Arianna L.; Spiegelman, Vladimir; Bickers, David R.

In: Cancer Research, Vol. 74, No. 18, 29.08.2014, p. 4967-4975.

Research output: Contribution to journalReview article

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