结肠癌中FOXN3的缺失激活β-连环蛋白/TCF信号通路并促进癌细胞的生长和迁移。

Dai Yuedi, Wang Meixing, Wu Haixia, Xiao Mi, Liu Houbao, Zhang Dexiang

Department of Medical Oncology, Cancer Hospital of Fudan University, Minhang Branch, Shanghai 200240, China.

General Surgery Department, General Surgery Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Oncotarget. 2017 Feb 7;8(6):9783-9793. doi: 10.18632/oncotarget.14189.

Aberrant activation of beta-catenin/TCF is a hallmark of colon cancer. How the functions of nuclear localized beta-catenin are regulated is not fully understood. Here, it was found that FOXN3 (Forkhead box N3) was down-regulated in colon cancer tissues. Forced expression of FOXN3 inhibited the growth, migration and invasion of colon cancer cells, while knocking down the expression of FOXN3 promoted the growth, migration, invasion and metastasis of colon cancer cells. FOXN3 bind to beta-catenin and inhibited beta-catenin/TCF signaling by blocking the interaction between beta-catenin and TCF4. Taken together, these data demonstrated the suppressive roles of FOXN3 in the progression of colon cancer, and indicated that restoring the functions of FOXN3 would be a novel therapeutic strategy for colon cancer.

β-连环蛋白/TCF的异常激活是结肠癌的一个标志。核定位的β-连环蛋白的功能是如何被调控的尚未完全清楚。在此，研究发现FOXN3（叉头框N3）在结肠癌组织中表达下调。强制表达FOXN3可抑制结肠癌细胞的生长、迁移和侵袭，而敲低FOXN3的表达则促进结肠癌细胞的生长、迁移、侵袭和转移。FOXN3与β-连环蛋白结合，并通过阻断β-连环蛋白与TCF4之间的相互作用来抑制β-连环蛋白/TCF信号传导。综上所述，这些数据证明了FOXN3在结肠癌进展中的抑制作用，并表明恢复FOXN3的功能将是一种新的结肠癌治疗策略。