PMID- 25172843
OWN - NLM
STAT- MEDLINE
DCOM- 20150120
LR  - 20211021
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 74
IP  - 18
DP  - 2014 Sep 15
TI  - Sonic hedgehog signaling in Basal cell nevus syndrome.
PG  - 4967-75
LID - 10.1158/0008-5472.CAN-14-1666 [doi]
AB  - 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.
CI  - (c)2014 American Association for Cancer Research.
FAU - Athar, Mohammad
AU  - Athar M
AD  - Department of Dermatology, University of Alabama at Birmingham, Birmingham, 
      Alabama. mathar@uab.edu.
FAU - Li, Changzhao
AU  - Li C
AD  - Department of Dermatology, University of Alabama at Birmingham, Birmingham, 
      Alabama.
FAU - Kim, Arianna L
AU  - Kim AL
AD  - Columbia University Medical Center, Irving Cancer Research Center, New York, New 
      York.
FAU - Spiegelman, Vladimir S
AU  - Spiegelman VS
AD  - University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
FAU - Bickers, David R
AU  - Bickers DR
AD  - Columbia University Medical Center, Irving Cancer Research Center, New York, New 
      York.
LA  - eng
GR  - P30 AR044535/AR/NIAMS NIH HHS/United States
GR  - R01 ES020344/ES/NIEHS NIH HHS/United States
GR  - R01 CA138998/CA/NCI NIH HHS/United States
GR  - R21 ES017494/ES/NIEHS NIH HHS/United States
GR  - R21 AR 064595/AR/NIAMS NIH HHS/United States
GR  - R01 ES015323/ES/NIEHS NIH HHS/United States
GR  - R21 AR064595/AR/NIAMS NIH HHS/United States
GR  - R01 AR063361/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20140829
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - Basal Cell Nevus Syndrome/drug therapy/genetics/*metabolism/pathology
MH  - Cell Growth Processes/physiology
MH  - Disease Models, Animal
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - Receptors, Cell Surface/metabolism
MH  - Signal Transduction
PMC - PMC4167483
MID - NIHMS615540
COIS- Conflict of interest: The authors disclose no potential conflicts of interest
EDAT- 2014/08/31 06:00
MHDA- 2015/01/21 06:00
PMCR- 2015/09/15
CRDT- 2014/08/31 06:00
PHST- 2014/08/31 06:00 [entrez]
PHST- 2014/08/31 06:00 [pubmed]
PHST- 2015/01/21 06:00 [medline]
PHST- 2015/09/15 00:00 [pmc-release]
AID - 0008-5472.CAN-14-1666 [pii]
AID - 10.1158/0008-5472.CAN-14-1666 [doi]
PST - ppublish
SO  - Cancer Res. 2014 Sep 15;74(18):4967-75. doi: 10.1158/0008-5472.CAN-14-1666. Epub 
      2014 Aug 29.