Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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The Role of Snail in EMT and Tumorigenesis

Author(s): Yifan Wang, Jian Shi, Kequn Chai, Xuhua Ying, Binhua P. Zhou.

Abstract:

Epithelial-mesenchymal transition (EMT) is a highly conserved process in which polarized, immobile epithelial cells lose tight junctions, associated adherence, and become migratory mesenchymal cells. Several transcription factors, including the Snail/Slug family, Twist, δEF1/ZEB1, SIP1/ZEB2 and E12/E47 respond to microenvironmental stimuli and function as molecular switches for the EMT program. Snail is a zinc-finger transcriptional repressor controlling EMT during embryogenesis and tumor progression. Through its N-terminal SNAG domain, Snail interacts with several corepressors and epigenetic remodeling complexes to repress specific target genes, such as the E-cadherin gene (CDH1). An integrated and complex signaling network, including the RTKs, TGF-β, Notch, Wnt, TNF-α, and BMPs pathways, activates Snail, thereby inducing EMT. Snail expression correlates with the tumor grade, nodal metastasis of many types of tumor and predicts a poor outcome in patients with metastatic cancer. Emerging evidences indicate that Snail causes a metabolic reprogramming, bestows tumor cells with cancer stem cell-like traits, and additionally, promotes drug resistance, tumor recurrence and metastasis. Despite many new and exciting developments, several challenges remain to be addressed in order to understand more thoroughly the role of Snail in metastasis. Additional investigations are required to disclose the contribution of microenvironmental factors on tumor progression. This information will lead to a comprehensive understanding of Snail in cancer and will provide us with novel approaches for preventing and treating metastatic cancers.

Keywords: Breast cancer, EMT, metastasis, signaling pathway, snail.

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Article Details

VOLUME: 13
ISSUE: 9
Year: 2013
Page: [963 - 972]
Pages: 10
DOI: 10.2174/15680096113136660102
Price: $58