Here, we reveal, for the first time, that the EMT inducer MDK, is a common responsive target of IFN-γ in all examined five cancer cell lines, and that MDK confers the pro-metastatic function of IFN-γ in these cell lines by activating the EMT programme; while pharmacologically targeting MDK using a specific inhibitor globally attenuated IFN-γ treatment-induced EMT and metastasis in all examined cancers. Here, MDK is linked to cancer.