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Review
. 2016 Dec 9;15(1):80.
doi: 10.1186/s12943-016-0566-7.

NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

Tingting Huang  1   2   3   4 , Yuhang Zhou  1   2   3 , Alfred S L Cheng  2   4   5 , Jun Yu  2   4   6 , Ka Fai To  7   8   9   10 , Wei Kang  11   12   13   14
Affiliations
Review

NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

Tingting Huang et al. Mol Cancer. .

Abstract

Gastric cancer (GC) ranks the most common cancer types and is one of the leading causes of cancer-related death. Due to delayed diagnosis and high metastatic frequency, 5-year survival rate of GC is rather low. It is a complex disease resulting from the interaction between environmental factors and host genetic alterations that deregulate multiple signaling pathways. The Notch signaling pathway, a highly conserved system in the regulation of the fate in several cell types, plays a pivotal role in cell differentiation, survival and proliferation. Notch is also one of the most commonly activated signaling pathways in tumors and its aberrant activation plays a key role in cancer advancement. Whether Notch cascade exerts oncogenic or tumor suppressive function in different cancer types depends on the cellular context. Mammals have four NOTCH receptors that modulate Notch pathway activity. In this review, we provide a comprehensive summary on the functional role of NOTCH receptors in gastric and other gastrointestinal cancers. Increasing knowledge of NOTCH receptors in gastrointestinal cancers will help us recognize the underlying mechanisms of Notch signaling and develop novel therapeutic strategies for GC.

Keywords: Gastric cancer; NOTCH receptors; Notch pathway.

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Figures

Fig. 1
Fig. 1
Schematic representation of Notch signaling cascade in GC cells. Notch signaling is initiated by ligand (DLL1/3/4 or JAG1/2) binding to NOTCH receptors (NOTCH1-4). Then a series of proteolytic cleavages occur, resulting in the release of NICDs. NICDs are translocated to the nucleus and bind with CSL to activate the expression of Notch downstream targets. The downstream proteins, such as COX-2, HES-1, Twist and CD133, promote cell proliferation, inhibit cell apoptosis and maintain cancer stem-like phenotypes. CSL, C protein binding factor 1/Suppressor of Hairless/Lag-1; NICD, Notch intracellular domain; TSS, transcription start site
Fig. 2
Fig. 2
The genetic alteration rates of NOTCH1-4 in GC from TCGA cohort. The bar chart indicates the amplification, deep deletion, mutation, mRNA upregulation rates of NOTCH1-4 in primary GC samples
See this image and copyright information in PMC

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