Transforming growth factor-beta signaling network regulates plasticity and lineage commitment of lung cancer cells
Authors
I Ischenko, J Liu, O Petrenko and MJ Hayman
Institution
Stony Brook
Country
United States
Year
2014
Journal
Cell Death & Differentiation
Abstract
Identification of target cells in lung tumorigenesis and characterization of the signals that control their behavior is an important
step toward improving early cancer diagnosis and predicting tumor behavior. We identified a population of cells in the adult lung
that bear the EpCAMþCD104þCD49fþCD44þCD24loSCA1þ phenotype and can be clonally expanded in culture,
consistent with the properties of early progenitor cells. We show that these cells, rather than being restricted to one tumor type,
can give rise to several different types of cancer, including adenocarcinoma and squamous cell carcinoma. We further
demonstrate that these cells can be converted from one cancer type to the other, and this plasticity is determined by their
responsiveness to transforming growth factor (TGF)-beta signaling. Our data establish a mechanistic link between TGF-beta
signaling and SOX2 expression, and identify the TGF-beta/SMAD/SOX2 signaling network as a key regulator of lineage
commitment and differentiation of lung cancer cells.