SMAD signaling promotes melanoma metastasis independently of phenotype switching.

ABSTRACT: The development of metastatic melanoma is thought to require the dynamic shifting of neoplastic cells between proliferative and invasive phenotypes. Contrary to this conventional "phenotype switching" model, we now show that disease progression can involve malignant melanoma cells simultaneously displaying proliferative and invasive properties. Using a genetic mouse model of melanoma in combination with in vitro analyses of melanoma cell lines, we found that conditional deletion of the downstream signaling molecule Smad4, which abrogates all canonical TGF-β signaling, indeed inhibits both tumor growth and metastasis. Conditional deletion of the inhibitory signaling factor Smad7, however, generated cells that are both highly invasive and proliferative, indicating that invasiveness is compat

SUBMITTER: Tuncer E 

PROVIDER: S-EPMC6597210 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature