Journal
NATURE MEDICINE
Volume 15, Issue 9, Pages 1055-U109Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2011
Keywords
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Funding
- US National Institutes of Health [RO1AR054396, RO1CA087837]
- Burroughs Wellcome Fund
- Packard Foundation
- Sandler Family Supporting Foundation
- A.P. Giannini Foundation
- Herbert W. Boyer Fund
- American Cancer Society
- NATIONAL CANCER INSTITUTE [R01CA087837, P30CA046592] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR045973, R01AR054396] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK074038] Funding Source: NIH RePORTER
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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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