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Nat Med. 2009 Sep;15(9):1055-61. doi: 10.1038/nm.2011. Epub 2009 Aug 23.

Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis.

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1
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California, USA.

Abstract

Primary cilia are present on most mammalian cells and are implicated in transducing Hedgehog (Hh) signals during development; however, the prevalence of cilia on human tumors remains unclear, and the role of cilia in cancer has not been examined. Here we show that human basal cell carcinomas (BCCs) are frequently ciliated, and we test the role of cilia in BCC by conditionally deleting Kif3a (encoding kinesin family member 3A) or Ift88 (encoding intraflagellar transport protein 88), genes required for ciliogenesis, in two Hh pathway-dependent mouse tumor models. Ciliary ablation strongly inhibited BCC-like tumors induced by an activated form of Smoothened. In contrast, removal of cilia accelerated tumors induced by activated Gli2, a transcriptional effector of Hh signaling. These seemingly paradoxical effects are consistent with a dual role for cilia in mediating both the activation and the repression of the Hh signaling pathway. Our findings demonstrate that cilia function as unique signaling organelles that can either mediate or suppress tumorigenesis depending on the nature of the oncogenic initiating event.

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PMID:
19701205
PMCID:
PMC2895420
DOI:
10.1038/nm.2011
[Indexed for MEDLINE]
Free PMC Article

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