C-kit induces epithelial–mesenchymal transition and contributes to salivary adenoid cystic cancer progression

Abstract

Epithelial–mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133+/CD44+ cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-β to contribute to EMT. c-kit itself was induced by TGF-β in ACC cell lines and required for TGF-β–induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.