Wnt/β-连环蛋白信号通路与上皮-间质转化（EMT）通路之间的相互作用介导了肾细胞癌中舒尼替尼耐药的机制。
Interaction between Wnt/β-catenin signaling pathway and EMT pathway mediates the mechanism of sunitinib resistance in renal cell carcinoma.
作者信息
Cai Fangzhen, Li Jianwei, Zhang Yanmei, Huang Sihuai, Liu Wenbin, Zhuo Weifeng, Qiu Chengzhi
机构信息
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Department of Urology, JinJiang Municipal Hospital, Quanzhou, Fujian, China.
出版信息
BMC Cancer. 2024 Feb 5;24(1):175. doi: 10.1186/s12885-024-11907-5.
BACKGROUND
Targeted drugs are the main methods of RCC treatment. However, drug resistance is common in RCC patients, in-depth study of the drug-resistant mechanism is essential.
METHODS
We constructed sunitinib resistant and Twist overexpressed A498 cells, and studied its mechanisms in vitro and in vivo.
RESULTS
In cell research, we found that either sunitinib resistance or Twist overexpression can activate Wnt/β-catenin and EMT signaling pathway, and the sunitinib resistance may work through β-catenin/TWIST/TCF4 trimer. In zebrafish research, we confirmed the similarity of Twist overexpression and sunitinib resistance, and the promoting effect of Twist overexpression on drug resistance.
CONCLUSIONS
Sunitinib resistance and Twist overexpression can activate Wnt/β-catenin signaling pathway and EMT to promote the growth and metastasis of RCC cells.
背景
靶向药物是肾细胞癌（RCC）治疗的主要方法。然而，耐药性在RCC患者中很常见，深入研究耐药机制至关重要。
方法
我们构建了舒尼替尼耐药且Twist过表达的A498细胞，并在体外和体内研究其机制。
结果
在细胞研究中，我们发现舒尼替尼耐药或Twist过表达均可激活Wnt/β-连环蛋白和上皮-间质转化（EMT）信号通路，且舒尼替尼耐药可能通过β-连环蛋白/TWIST/TCF4三聚体起作用。在斑马鱼研究中，我们证实了Twist过表达与舒尼替尼耐药的相似性，以及Twist过表达对耐药性的促进作用。
结论
舒尼替尼耐药和Twist过表达可激活Wnt/β-连环蛋白信号通路和EMT，以促进RCC细胞的生长和转移。
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