Multilevel regulation of Wnt signaling by Zic2 in colon cancer due to mutation of β-catenin

• DOI: 10.1038/s41419-021-03863-w
• Publication Date: 2021-06-07T11:02:58Z
• Authors: Zhengshui Xu; Jianbao Zheng; Zilu Chen; Jing Guo; Xiaopeng Li; Xingjie Wang; Chao Qu; Liyue Yuan; Chen Cheng; Xuejun Sun; Junhui Yu
• Keywords: AXIN2; Ectopic expression; Beta-catenin

Abstract Zinc-finger of the cerebellum 2 (Zic2) is widely implicated in cancers, but role Zic2 tumorigenesis bilateral. A recent study indicated that could render colon cancer cells more resistant to low glucose-induced apoptosis. However, functional roles and underlying molecular mechanism remain elusive. Herein, we demonstrated was highly expressed tissues correlated with poor survival. Knockdown inhibited cell growth, arrested cycle transition from G0/G1 S phase, suppressed tumor sphere formation vitro; addition, silencing retarded xenograft vivo. Consistently, ectopic expression had opposite effects. Mechanistically, executed its oncogenic by enhancing Wnt/β-catenin signaling. directly binds promoter Axin2 transcriptionally represses subsequently promotes accumulation nuclear translocation β-catenin. Meanwhile, activate Wnt signaling interacting Intriguingly, HCT116 intrinsic Ser45 mutation β-catenin, which blocks degradation-related phosphorylation β-catenin CK1, modified did not affect protein level Altogether, our findings uncover a novel multilevel for activity suggest as potential therapeutic target patients.