miR-9, a miRNA activated by MYC and MYCN, regulates E-cadherin and cancer metastasis. The study shows that miR-9 directly targets the E-cadherin-encoding mRNA, CDH1, leading to reduced E-cadherin expression and increased cell motility and invasiveness. This downregulation of E-cadherin activates β-catenin signaling, which increases vascular endothelial growth factor (VEGF) expression, promoting tumor angiogenesis. Overexpression of miR-9 in non-metastatic breast tumor cells enables them to form pulmonary micrometastases in mice, while inhibiting miR-9 reduces metastasis. miR-9 expression is activated by MYC and MYCN, which directly bind to the mir-9-3 locus. In human cancers, miR-9 levels correlate with MYCN amplification, tumor grade, and metastatic status. These findings reveal a regulatory pathway involving miR-9, which promotes metastasis by targeting E-cadherin, a key metastasis suppressor. The study also shows that miR-9 induces EMT, enhances tumor angiogenesis, and promotes metastasis. miR-9 silencing reduces metastasis formation in highly malignant cancer cells. miR-9 expression is regulated by MYC and MYCN, which bind to the mir-9-3 locus. miR-9 expression is upregulated in breast tumors with high MYCN amplification and metastatic status. The study highlights the role of miR-9 in cancer progression and metastasis, emphasizing its potential as a therapeutic target.miR-9, a miRNA activated by MYC and MYCN, regulates E-cadherin and cancer metastasis. The study shows that miR-9 directly targets the E-cadherin-encoding mRNA, CDH1, leading to reduced E-cadherin expression and increased cell motility and invasiveness. This downregulation of E-cadherin activates β-catenin signaling, which increases vascular endothelial growth factor (VEGF) expression, promoting tumor angiogenesis. Overexpression of miR-9 in non-metastatic breast tumor cells enables them to form pulmonary micrometastases in mice, while inhibiting miR-9 reduces metastasis. miR-9 expression is activated by MYC and MYCN, which directly bind to the mir-9-3 locus. In human cancers, miR-9 levels correlate with MYCN amplification, tumor grade, and metastatic status. These findings reveal a regulatory pathway involving miR-9, which promotes metastasis by targeting E-cadherin, a key metastasis suppressor. The study also shows that miR-9 induces EMT, enhances tumor angiogenesis, and promotes metastasis. miR-9 silencing reduces metastasis formation in highly malignant cancer cells. miR-9 expression is regulated by MYC and MYCN, which bind to the mir-9-3 locus. miR-9 expression is upregulated in breast tumors with high MYCN amplification and metastatic status. The study highlights the role of miR-9 in cancer progression and metastasis, emphasizing its potential as a therapeutic target.