TIPE inhibits ferroptosis in colorectal cancer cells by regulating MGST1/ALOX5.

Abstract

TIPE is a protein highly expressed in various cancers that promotes ferroptosis in colorectal cancer (CRC) cells. Ferroptosis is a non-apoptotic cell death caused by lipid peroxidation, and MGST1 is a critical enzyme that resists lipid peroxidation. This study explored how TIPE regulates MGST1 expression to inhibit ferroptosis and promote CRC proliferation. TIPE was highly expressed in CRC tissues and positively correlated with the proliferation of human CRC cells. We measured levels of reactive oxygen species (ROS) and lipid-ROS in CRC cells with differential expression of TIPE and detected ferroptosis using transmission electron microscopy. Bioinformatics analysis revealed a positive correlation of expression patterns between TIPE and MGST1 in CRC. TIPE regulated the expression of MGST1 by activating the phosphorylation of ERK1/2. Co-immunoprecipitation revealed binding between MGST1 and ALOX5. This binding inhibited the phosphorylation of ALOX5, inhibiting ferroptosis and promoting the proliferation of CRC cells. A tumor formation experiment in nude mice supported our findings that TIPE regulates the proliferation of CRC by regulating ferroptosis. Implications: TIPE inhibits CRC ferroptosis via an MGST1-ALOX5 interaction to promote CRC proliferation. These findings suggest future CRC treatment strategies.