作者: Lidia Avalle , Danny Incarnato , Aurora Savino , Marta Gai , Francesca Marino
DOI: 10.1038/CDD.2017.103
关键词: STAT3 、 Cell biology 、 Regulation of gene expression 、 Cell migration 、 Biology 、 Transcription factor 、 Transforming growth factor 、 SMAD 、 Epithelial–mesenchymal transition 、 Tumor progression
摘要: Transforming growth factor (TGF)-β is one of the major inducers epithelial to mesenchymal transition (EMT), a crucial program that has critical role in promoting carcinoma’s metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, essential for differentiation vascular smooth muscle cells (VSMC) during embryogenesis, TGF-β-dependent process reminiscent EMT. Their adult tissues however less well defined even ambiguous, as their expression was correlated positively negatively with tumor progression. Here we show high miRs-143 -145 mouse mammary expressing constitutively active STAT3 (S3C) involved mediating disrupted cell–cell junctions. Additionally, miR-143 appears have unique tumorigenesis by enhancing cell migration vitro extravasation vivo while impairing anchorage-independent growth, may explain contradictory reports about its tumors. Accordingly, demonstrate overexpression either miRNA non-transformed NMuMG leads upregulation EMT markers several endogenous downmodulation number junction proteins increased motility, correlating enhanced basal TGF-β-induced SMAD-mediated transcription. Moreover, pervasive transcriptome perturbation consistent described phenotype observed. In particular, transcription factors mitogenic responses, MAPK family members and, importantly, tight SMAD co-repressor TGIF significantly reduced. Our results provide important mechanistic insight into non-redundant EMT-related processes transformed cells, suggest must be finely coordinated warrant optimal migration/invasion not interfering growth.