Together, our data indicate that TRIM59 promotes breast cancer cell metastasis by (1) inhibiting the phosphorylation of MLC and ERM required for actomyosin contractility and amoeboid migration, (2) reducing the expression of cell adhesion molecules such as E-cadherin, and (3) increasing the cellular level of β-catenin and promoting metastasis-associated Wnt signaling. The gene discussed is MLC1; the disease is breast cancer.