| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2042279 | Cell Reports | 2014 | 14 Pages |
•miR-203 regulates in vivo lung metastasis without triggering differentiation•Restoring miR-203 in already established metastases elicits regression•LASP1, NUAK1, and SPARC are downstream prometastatic effectors of miR-203•The miR-203-LASP1/SPARC/NUAK1 axis is prognostic of overall survival in HNSCC
SummaryMetastatic colonization of distant organs underpins the majority of human-cancer-related deaths, including deaths from head and neck squamous cell carcinoma (HNSCC). We report that miR-203, a miRNA that triggers differentiation in multilayered epithelia, inhibits multiple postextravasation events during HNSCC lung metastasis. Inducible reactivation of miR-203 in already established lung metastases reduces the overall metastatic burden. Using an integrated approach, we reveal that miR-203 inhibits metastasis independently of its effects on differentiation. In vivo genetic reconstitution experiments show that miR-203 inhibits lung metastasis by suppressing the prometastatic activities of three factors involved in cytoskeletal dynamics (LASP1), extracellular matrix remodeling (SPARC), and cell metabolism (NUAK1). Expression of miR-203 and its downstream effectors correlates with HNSCC overall survival outcomes, indicating the therapeutic potential of targeting this signaling axis.
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