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Publication : Transforming growth factor-beta signaling network regulates plasticity and lineage commitment of lung cancer cells.

First Author  Ischenko I Year  2014
Journal  Cell Death Differ Volume  21
Issue  8 Pages  1218-28
PubMed ID  24682004 Mgi Jnum  J:229788
Mgi Id  MGI:5754462 Doi  10.1038/cdd.2014.38
Citation  Ischenko I, et al. (2014) Transforming growth factor-beta signaling network regulates plasticity and lineage commitment of lung cancer cells. Cell Death Differ 21(8):1218-28
abstractText  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 EpCAM+CD104+CD49f+CD44+CD24loSCA1+ 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.
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