Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer
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- 5 March 2003
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 422 (6929), 313-317
- https://doi.org/10.1038/nature01493
Abstract
Embryonic signalling pathways regulate progenitor cell fates in mammalian epithelial development and cancer. Prompted by the requirement for sonic hedgehog (Shh) signalling in lung development, we investigated a role for this pathway in regeneration and carcinogenesis of airway epithelium. Here we demonstrate extensive activation of the hedgehog (Hh) pathway within the airway epithelium during repair of acute airway injury. This mode of Hh signalling is characterized by the elaboration and reception of the Shh signal within the epithelial compartment, and immediately precedes neuroendocrine differentiation. We reveal a similar pattern of Hh signalling in airway development during normal differentiation of pulmonary neuroendocrine precursor cells, and in a subset of small-cell lung cancer (SCLC), a highly aggressive and frequently lethal human tumour with primitive neuroendocrine features. These tumours maintain their malignant phenotype in vitro and in vivo through ligand-dependent Hh pathway activation. We propose that some types of SCLC might recapitulate a critical, Hh-regulated event in airway epithelial differentiation. This requirement for Hh pathway activation identifies a common lethal malignancy that may respond to pharmacological blockade of the Hh signalling pathway.Keywords
This publication has 29 references indexed in Scilit:
- Molecular Pathogenesis of Lung CancerAnnual Review of Physiology, 2002
- Stem cells, cancer, and cancer stem cellsNature, 2001
- The Hedgehog and Wnt signalling pathways in cancerNature, 2001
- Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamineNature, 2000
- Neuroepithelial Bodies of Pulmonary Airways Serve as a Reservoir of Progenitor Cells Capable of Epithelial RegenerationThe American Journal of Pathology, 2000
- Alteration of Pulmonary Neuroendocrine Cells during Epithelial Repair of Naphthalene-Induced Airway InjuryThe American Journal of Pathology, 2000
- Sonic hedgehog is essential to foregut developmentNature Genetics, 1998
- Sonic hedgehog regulates branching morphogenesis in the mammalian lungCurrent Biology, 1998
- Altered Neural Cell Fates and Medulloblastoma in Mouse patched MutantsScience, 1997
- Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron IdentityCell, 1996