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-? to contribute to EMT. c-kit itself was induced by TGF-? in ACC cell lines and required for TGF-?-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.

SUBMITTER: Tang YL 

PROVIDER: S-EPMC4039226 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other