Based junction formation and inhibit cell migration in Boyden-type transwell chambers. It appears that the miR-200 family is targeting Zeb transcriptional regulators, particularly Zeb1, preventing the repression of E-cadherin expression by Zeb proteins. Because miR-200 levels are decreased in more aggressive metaplastic Fulvestrant breast as compared with ductal tumors, and EMT is associated with disruption of cell-cell adhesion and the acquisition of migratory behavior, it has been suggested that the miR-200 down-regulation is involved with the progression of cancer through promoting EMT and cell invasion. However, while the expression of miR-200 family members is down-regulated in some types of cancer, these microRNAs are over-expressed in other cancers such as melanoma, ovarian and colorectal cancers. For example, miR-200c is up-regulated in melanoma lines compared to normal melanocytes and in primary melanoma as compared to benign nevi. Additionally, analysis of microRNA levels showed that miR200c was up-regulated in melanoma metastases to the lung, although down-regulated in those to the brain, as compared to primary lesions. Taken together, this data suggests that miR200c is differentially regulated in melanoma and may play a role in disease initiation and/or progression. In order to investigate the functional effects of the miR-200 family in melanoma, we decided to test whether expression of miR-200 family members affects the ability of melanoma cells to engage in morphological switching and use different modes of migration to invade into a physiologic 3D collagen-I matrix. We confirmed that miR-200 members are up-regulated in melanoma, show they do not suppress invasion into 3D matrices and sometimes increase invasive capacity. Interestingly, while elevation of miR-200a levels led to the mesenchymal mode of cell migration, elevation of miR-200c levels led to the amoeboid mode of migration, highlighting new roles of this microRNA family in switching or plasticity of modes of tumor cell migration. The results presented here suggest that the miR-200 family of microRNAs regulates melanoma cell morphology and associated invasion, and that functional differences exist between different miR-200 family members. Deregulation of miR-200 expression has been observed in multiple cancer studies, and this group of microRNAs has been shown to be up-regulated in some, but down-regulated in other types of cancer. The majority of functional studies, particularly in breast cancer have concentrated on roles of down-regulation, suggesting that miR-200 members prevent tumor progression by negatively regulating Zeb transcriptional repressors and consequently maintaining Ecadherin junctions and preventing EMT. Up-regulation of miR200 members has however been identified in cancer of the ovaries, cervix, bowel, melanocyte lineage, bile duct, and prostate as well as in cancer models. These findings suggest that miR-200 regulation and activity may be highly context-dependent and that miR-200 may be promoting progression of some cancers.