Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215000, China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
Aging (Albany NY). 2023 Apr 14;15(8):3035-3051. doi: 10.18632/aging.204656.
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. 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.
结直肠癌（CRC）是全球癌症死亡的主要原因。尽管在 CRC 治疗方面取得了相当大的进展，但有效的治疗改善已经遇到了瓶颈。本研究表明，TYRO3 表达在具有预后相关性的 CRC 组织中异常增加。基于 TYRO3 表达构建了 CRC 患者预后的预测模型。该模型表明 TYRO3 水平对最终预测结果至关重要。我们观察到通过构建耐药 CRC 细胞系敲低 TYRO3 表达可以抑制增殖和迁移能力并逆转耐药性。实验也证实了这一结论。因此，靶向 TYRO3 联合 5-Fu 治疗可能提供更好的治疗效果。此外，TYRO3 可以通过下调 ENO1 抑制 EMT 过程，这可能是通过干扰癌细胞的能量代谢来实现的。因此，本研究为 TYRO3 在 CRC 细胞耐药性中的作用提供了理论依据，并强调了 CRC 靶向治疗的新策略。
