RIPK4 driven by TP53 mutations promotes resistance to PANoptosis and metastasis of CRC by phosphorylation of MTHFD1 [Anokis_seq]

In this study, we found that RIPK4 protein driven by TP53 mutation is highly expressed in CRC, which can promote the phosphorylation level of MTHFD1 (Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase And Formyltetrahydrofolate Synthetase 1), a key enzyme of carbon metabolism, promote the generation of NADPH in CRC cells, and reduce the level of ROS, thus promoting PANoptosis resistance and distant metastasis of CRC cells. We explain the novel mechanism of metastasis induced by the TP53 mutation in terms of post-translational modification and clarify the biological role of the RIPK4 protein in CRC, which can be used as a new target for the treatment of metastatic CRC.