Abstract
Gastrointestinal (GI) cancer is characterized by its aggressiveness, but the underlying mechanism is not fully understood. Studies reveal that epithelial to mesenchymal transition (EMT), which is regulated by a series of transcription factors and signaling pathways, is strongly associated with GI cancer cell proliferation, invasion and metastasis. Importantly, EMT is a product of crosstalk between signaling pathways. Krüppel-like factor 4 (KLF4), a zinc finger-type transcription factor, is decreased or lost in most GI cancers. By transcriptionally regulating its downstream target genes, KLF4 plays important roles of GI cancer tumorigenesis, proliferation and differentiation. In this review, we focus on the mechanism of KLF4 in GI cancer EMT, and demonstrate that through crosstalk with TGF-β, Notch, and Wnt signaling pathways, KLF4 negatively regulates EMT of GI cancers. Finally, we indicate the challenging new frontiers for KLF4 which contributes to better understanding of the mechanism of GI cancer aggressiveness.
Keywords: EMT, gastrointestinal cancer, KLF4, Notch, TGF-β, Wnt.
Current Cancer Drug Targets
Title:Regulation of EMT by KLF4 in Gastrointestinal Cancer
Volume: 13 Issue: 9
Author(s): Jiujie Cui, Min Shi, Ming Quan and Keping Xie
Affiliation:
Keywords: EMT, gastrointestinal cancer, KLF4, Notch, TGF-β, Wnt.
Abstract: Gastrointestinal (GI) cancer is characterized by its aggressiveness, but the underlying mechanism is not fully understood. Studies reveal that epithelial to mesenchymal transition (EMT), which is regulated by a series of transcription factors and signaling pathways, is strongly associated with GI cancer cell proliferation, invasion and metastasis. Importantly, EMT is a product of crosstalk between signaling pathways. Krüppel-like factor 4 (KLF4), a zinc finger-type transcription factor, is decreased or lost in most GI cancers. By transcriptionally regulating its downstream target genes, KLF4 plays important roles of GI cancer tumorigenesis, proliferation and differentiation. In this review, we focus on the mechanism of KLF4 in GI cancer EMT, and demonstrate that through crosstalk with TGF-β, Notch, and Wnt signaling pathways, KLF4 negatively regulates EMT of GI cancers. Finally, we indicate the challenging new frontiers for KLF4 which contributes to better understanding of the mechanism of GI cancer aggressiveness.
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Cite this article as:
Cui Jiujie, Shi Min, Quan Ming and Xie Keping, Regulation of EMT by KLF4 in Gastrointestinal Cancer, Current Cancer Drug Targets 2013; 13 (9) . https://dx.doi.org/10.2174/15680096113136660104
DOI https://dx.doi.org/10.2174/15680096113136660104 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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