MT1H Inhibited Colon Cancer Development via Interacting With DUSP1 and MAPK Signaling Pathway Inactivation

We focused on examining the impact of metallothionein 1H (MT1H) on colon cancer (CC) proliferation, migration, and invasion, as well as elucidating its underlying molecular mechanisms. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The invasive and migratory capacities of the cells were evaluated through transwell and wound healing assays. We found that both MT1H were lowly expressed in human CC tissues by immunohistochemistry (IHC). In HCT116 and SW480 cells and a xenograft mouse model, we found that overexpression of MT1H could inhibit CC cell proliferation, migration, and invasion. In HCT116 and SW480 cell lines, as well as in a xenograft mouse model, our study demonstrated that the overexpression of MT1H significantly inhibited CC cell proliferation, migration, and invasion. Subsequent analyses revealed that MT1H interacts with dual-specificity phosphatase 1 (DUSP1) and enhances its expression. Further investigation into the role of DUSP1 in modulating the biological behavior of CC cells indicated that the suppression of proliferation, migration, and invasion induced by MT1H overexpression was reversed upon DUSP1 knockdown. Mechanically, we further showed MT1H overexpression suppressed mitogen-activated protein kinase (MAPK) signaling and the expression of downstream proteins extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, which were blocked by DUSP1 knockdown. Moreover, our investigation revealed that the inhibition of the MAPK signaling pathway counteracted the impact of MT1H overexpression on CC cell proliferation, migration, and invasion. Taken together, these results suggest MT1H expression hinders CC progression by interacting with DUSP1 and subsequently deactivating the MAPK signaling. MT1H might be a novel target in CC treatment.