Cell-type restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing

ABSTRACT: Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein hnRNPM promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFb signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFb-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44s splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the

ORGANISM(S): Homo sapiens

SUBMITTER: Xu Y 

PROVIDER: S-ECPF-GEOD-57243 | biostudies-other | 2014 Jun

REPOSITORIES: biostudies-other