Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer

D. Neil Watkins, David M. Berman, Scott G. Burkholder, Baolin Wang, Philip A. Beachy, Stephen B Baylin

Research output: Contribution to journalArticle

Abstract

Embryonic signalling pathways regulate progenitor cell fates in mammalian epithelial development and cancer1,2. Prompted by the requirement for sonic hedgehog (Shh) signalling in lung development3,4, 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.

Original languageEnglish (US)
Pages (from-to)313-317
Number of pages5
JournalNature
Volume422
Issue number6929
DOIs
StatePublished - Mar 20 2003

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Small Cell Lung Carcinoma
Epithelium
Neoplasms
Neuroendocrine Cells
Lung
Regeneration
Carcinogenesis
Stem Cells
Pharmacology
Ligands
Phenotype
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Watkins, D. N., Berman, D. M., Burkholder, S. G., Wang, B., Beachy, P. A., & Baylin, S. B. (2003). Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature, 422(6929), 313-317. https://doi.org/10.1038/nature01493

Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. / Watkins, D. Neil; Berman, David M.; Burkholder, Scott G.; Wang, Baolin; Beachy, Philip A.; Baylin, Stephen B.

In: Nature, Vol. 422, No. 6929, 20.03.2003, p. 313-317.

Research output: Contribution to journalArticle

Watkins, DN, Berman, DM, Burkholder, SG, Wang, B, Beachy, PA & Baylin, SB 2003, 'Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer', Nature, vol. 422, no. 6929, pp. 313-317. https://doi.org/10.1038/nature01493
Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003 Mar 20;422(6929):313-317. https://doi.org/10.1038/nature01493
Watkins, D. Neil ; Berman, David M. ; Burkholder, Scott G. ; Wang, Baolin ; Beachy, Philip A. ; Baylin, Stephen B. / Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. In: Nature. 2003 ; Vol. 422, No. 6929. pp. 313-317.
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