MMP1 and colonic neoplasm: Furthermore, we demonstrated that USP21 is oncogenic in colorectal cancers by positively regulating Fra-1 activity as a Fra-1 DUB and increasing the expression of MMP-1, the Fra-1 target gene, as summarized in Figure 7D. We demonstrated that USP21 level was highly associated with tumor formation and metastasis both in colon cancer cells and in the animal model, consistent with our findings that CRC tissues highly expressed USP21 and USP21 expression was correlated with tumor progression.