Wang Ji-Lian, Qi Zhen, Li Ye-Hua, Zhao Hong-Mei, Chen Ye-Guang, Fu Wei
Department of General Surgery, Peking University Third Hospital, Beijing 100191, China.
The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Oncotarget. 2017 Jul 26;8(41):70214-70225. doi: 10.18632/oncotarget.19603. eCollection 2017 Sep 19.
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 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 and . In addition, TGIF1 activates Wnt/β-catenin signaling, and the homeodomain is indispensable for Wnt activation and β-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.
结直肠癌（CRC）是最常见的癌症之一，但其发生和发展的潜在机制在很大程度上尚不清楚。TGIF1（转化生长因子β诱导因子同源框1）是一种转录共抑制因子，属于非典型同源结构域的三氨基酸环延伸（TALE）超家族。据报道，TGIF1在乳腺癌和非小细胞肺癌中高表达，并可促进肿瘤进展。然而，其在结直肠癌中的作用仍不清楚。在此，我们报告TGIF1在结直肠癌中显著上调，其高表达预示预后不良。TGIF1的过表达在体内和体外均显著促进结直肠癌细胞的增殖。此外，TGIF1激活Wnt/β-连环蛋白信号通路，且同源结构域对于Wnt激活和β-连环蛋白相互作用不可或缺。综上所述，我们的结果表明TGIF1是一种新型的结直肠肿瘤促进因子，并表明TGIF1通过激活Wnt信号通路增强结直肠癌的肿瘤发生。
