TYRO3 promotes tumorigenesis and drug resistance in colorectal cancer by enhancing the epithelial-mesenchymal transition process

Abstract

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.

Immune Checkpoint Inhibitors: A Narrative Review on PD-1/PD-L1 Blockade Mechanism, Efficacy, and Safety Profile in Treating Malignancy

“…High amounts of these reactive molecules activate lipid peroxidation, leading to the death of the tumor cell [ 51 ]. A study by Shao et al [ 52 ] revealed that TYRO3 expression was found to be increased in colorectal cancer cells, and blocking this receptor improved the efficacy of 5-fluorouracil treatment. The findings in this study further suggest that inhibiting TYRO3 may be another promising method to reduce cancer resistance to PD-1 therapy.…”