Xu Xiaoxiao, Duan Xiaofan, Wang Shunli, Zhang Yumei, Gao Yuan, Xu Xiaolin, Yeerkenbieke Gaoshaer, Zhou Jiuli, Li Jin
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
School of Medicine, Tongji University, Shanghai, China.
Int J Cancer. 2023 Jan 1;152(1):51-65. doi: 10.1002/ijc.34227. Epub 2022 Sep 2.
Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3β/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment.
肿瘤转移是结直肠癌（CRC）死亡率高的主要原因之一。然而，其潜在机制尚未完全明确。在此，我们报告称，与正常相邻组织相比，盘状结构域受体2（DDR2）在CRC组织中的表达显著上调。DDR2的表达水平与CRC患者的预后呈负相关。因此，DDR2可能在CRC发展中发挥致癌作用。此外，DDR2在CRC细胞中诱导上皮-间质转化，并在体外和体内调节其侵袭和转移能力。机制上，DDR2表达水平的升高激活了AKT/GSK-3β/Slug信号通路。总之，这些发现表明DDR2促进了CRC转移，抑制DDR2可能是局部晚期和转移性CRC治疗的有效策略。
