Updated project metadata. Colorectal cancer remains a public health issue and most of colon cancer patients succumb to the development of metastases. Using a specific protocol, we identified paladin as a potential colon cancer liver metastases biomarker. We then explored the biological function of paladin in colon cancer cells. We discovered that paladin is required for cell migration and metastasis. We reported that paladin depletion altered the phospho-proteome within colon cancer cells. Thanks to immuno-precipitation experiments, we demonstrated that paladin was interacting with SSH-1, a phosphatase involved in colon cancer metastasis. Finally, we showed that paladin depletion in cancer cells altered the interaction between SSH-1 and actin, which results in a less dynamic actin cytoskeleton. In conclusion, paladin is an under undervalued protein in oncology participating in actin cytoskeleton remodelling and necessary for an efficient cancer cell migration