Sonic hedgehog (Shh) is a mammalian hedgehog (Hh) pathway ligand that mediates epithelial–mesenchymal interactions in lung development. Loss of Shh function results in severe lung defects associated with failure of branching morphogenesis. However, the role of Shh in regeneration and carcinogenesis of airway epithelium is unknown. In the March 5 advanced online
Watkins et al. studied a murine model of acute airway repair and observed extensive activation of the Hh pathway within the airway epithelium during repair. In addition, they found a similar pattern of Hh signaling in a subset of small-cell lung cancer (SCLC) cells with primitive neuroendocrine features. These tumors maintained their malignant phenotype in vitro and in vivo through ligand-dependent Hh pathway activation.
"SCLC may represent a malignancy arising from an airway epithelial progenitor that retains both Hh signalling and primitive features of pulmonary neuroendocrine differentiation. The vulnerability of SCLC to Hh pathway blockade may represent a new therapeutic approach to a disease with a poor prognosis," conclude the authors.