TGFβ induced factor homeobox 1 promotes colorectal cancer development through activating Wnt/β-catenin signaling

被引:29
作者
Wang, Ji-Lian [1 ]
Qi, Zhen [2 ]
Li, Ye-Hua [2 ]
Zhao, Hong-Mei [1 ]
Chen, Ye-Guang [2 ]
Fu, Wei [1 ]
机构
[1] Peking Univ, Dept Gen Surg, Hosp 3, Beijing 100191, Peoples R China
[2] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China
基金
中国国家自然科学基金;
关键词
colorectal cancer; TGIF1; Wnt signaling; beta-catenin; TGF-beta; COLON-CANCER; MICROSATELLITE INSTABILITY; GENETIC INSTABILITY; COREPRESSOR TGIF; TALE SUPERCLASS; MUTATIONS; TARGET; ONCOGENES; PROTEIN; OCCUR;
D O I
10.18632/oncotarget.19603
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer (CRC) is one of the most common cancers, but the mechanisms underlying its initiation and progression are largely unknown. TGIF1 (TGFB induced factor homeobox 1) is a transcriptional corepressor that belongs to the three-amino acid loop extension (TALE) superclass of atypical homeodomains. It has been reported that TGIF1 is highly expressed in mammary cancer and non-small cell lung cancer and can enhance tumor progression. However, the role of TGIF1 in colorectal cancer remains unknown. Here, we report that TGIF1 is significantly upregulated in colorectal cancers, and its high expression predicts poor prognosis. Overexpression of TGIF1 markedly promotes the proliferation of colorectal cancer cells both in vivo and in vitro. In addition, TGIF1 activates Wnt/beta-catenin signaling, and the homeodomain is indispensable for Wnt activation and beta-catenin interaction. Taken together, our results suggest that TGIF1 is a novel colorectal tumor promoter and indicate that TGIF1 enhances colorectal cancer tumorigenesis through activating Wnt signaling.
引用
收藏
页码:70214 / 70225
页数:12
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