Achaete–scute homolog-1 and Notch in lung neuroendocrine development and cancer

Achaete–scute homolog-1 (termed Mash1 in rodents, hASH1 in humans) is a basic helix–loop–helix transcription factor important in early development of neural and neuroendocrine (NE) progenitor cells in multiple tissues including the CNS, autonomic nervous system, adrenal medulla, thyroid, lung, and prostate, among others. This review discusses how progress in developmental neurobiology of Mash1 has translated into novel insights in NE tumor biology, particularly for small cell lung cancer. Inhibition of this factor by the Notch pathway is essential in regulating NE commitment in airway epithelial precursor cells, and may play a comparable role in modulating phenotypes of lung cancer and other tumors.