Abstract
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/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.
Highlights
Colorectal cancer (CRC) is one of the most common cancers and has a high mortality rate in its later stage [1]
These results indicate that the nuclear TGFB induced factor homeobox 1 (TGIF1) may promote stemness of stem/progenitor cells at the base of crypts and enhance their tumorigenic ability during transformation
Our results indicate the TGIF1 is significantly upregulated in CRC tissues and may play important roles in tumorigenesis
Summary
Colorectal cancer (CRC) is one of the most common cancers and has a high mortality rate in its later stage [1]. Several factors are associated with the initiation and progression of CRC, including mutations in proto-oncogenes or tumor suppressor genes [2, 3], chromosomal instability and microsatellite instability [4,5,6] and epigenetic modifications [7]. Β-catenin translocates into the nucleus and acts with members of the T cell factor/lymphoid enhancer binding factor (TCF/ LEF) family to activate transcription of downstream genes including CCND1 and c-Myc, both of which are the cell cycle regulators upregulated in colorectal tumors [12,13,14,15]. Activation of Wnt signaling by gene mutations plays a crucial role in colorectal cancer development. Some of the Wnt target genes contribute to cancer progression [16]
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