Notch signaling: An emerging therapeutic target for cancer treatment

Yuan, Xun; Wu, Hua; Xu, Hanxiao; Xiong, Huihua; Chu, Qian; Yu, Shiying; Wu, Gen Sheng; Wu, Kongming

doi:10.1016/j.canlet.2015.07.048

Cited by 338 publications

(273 citation statements)

References 89 publications

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“…This will undoubtedly lead to novel drug candidates within the next decade. Moreover, phase I and II clinical trials with known GSIs aimed at inhibition of Notch signaling in cancer patients, often in combination with other treatments, have shown promise [50,51]. Hence, IMP inhibitors as drugs for treatment of human disease are on the horizon.…”

Section: Other Future Research Directions and Concluding Remarksmentioning

confidence: 99%

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Intramembrane proteases as drug targets

Verhelst

2017

The FEBS Journal

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Proteases are considered attractive drug targets. Various drugs targeting classical, soluble proteases have been approved for treatment of human disease. Intramembrane proteases (IMPs) are a more recently discovered group of proteolytic enzymes. They are embedded in lipid bilayers and their active sites are located in the plane of a membrane. All four mechanistic families of IMPs have been linked to disease, but currently, no drugs against IMPs have entered the market. In this review, I will outline the function of IMPs with a focus on the ones involved in human disease, which includes Alzheimer's disease, cancer, and infectious diseases by microorganisms. Inhibitors of IMPs are known for all mechanistic classes, but are not yet very potent or selective – aside from those targeting γ‐secretase. I will here describe the different features of IMP inhibitors and discuss a list of issues that need attention in the near future in order to improve the drug development for IMPs.

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Section: Other Future Research Directions and Concluding Remarksmentioning

confidence: 99%

“…However, increased Notch signaling has also been detected in many different solid tumors. Hence, molecules that inhibit Notch cleavage could potentially be used in cancer treatment [50,51], and several GSIs originally developed against AD are now in clinical trials against cancer.…”

Section: Aspartate Impsmentioning

confidence: 99%

Intramembrane proteases as drug targets

Verhelst

2017

The FEBS Journal

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“…JAG1, as a Notch ligand, was found to be upregulated in GC tissues compared with matched normal tissues in the present study. Notch signaling is a highly conserved cell-signaling pathway that is involved in cell proliferation, differentiation and survival (29). Dysregulation of the Notch signaling pathway often promotes tumor formation and progression.…”

Section: Discussionmentioning

confidence: 99%

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Chen

et al. 2018

Oncol Lett

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Abstract. expression is downregulated and has a tumor suppressor role in various types of cancer. The present study revealed that genes encoding miR-124 were frequently methylated and the expression of miR-124 was downregulated in gastric cancer tissues. Stable expression of miR-124 using a lentiviral vector inhibited gastric cancer cell growth, migration and invasion in vitro. In addition, overexpression of miR-124 suppressed gastric cancer cell xenograft growth in nude mice. The expression of the Notch ligand Jagged1 (JAG1) and enhancer of zeste homolog 2 (EZH2) was downregulated upon miR-124 overexpression, and silencing of JAG1 or EZH2 by RNA interference also suppressed gastric cancer cell growth, migration and invasion. Furthermore, expression of fibronectin and vimentin, not able elements of the epithelial-mesenchymal transition, were suppressed by overexpression of miR-124 or inhibition of JAG1 or EZH2 expressions in GC. Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer.

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“…Notch signaling is a highly conserved cell signaling pathway that is involved in multiple aspects of metazoan growth and development, including cell proliferation, differentiation and apoptosis (1). It has been suggested to be one of the most commonly activated signaling pathways in neoplastic diseases, most notably in gastrointestinal malignancies including stomach, colorectal and esophageal cancer, as well as liver and pancreatic cancers (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested to be one of the most commonly activated signaling pathways in neoplastic diseases, most notably in gastrointestinal malignancies including stomach, colorectal and esophageal cancer, as well as liver and pancreatic cancers (1)(2)(3). Furthermore, the abnormal activation of Notch signaling may result from the mutation or amplification of Notch signaling components (1). As Notch signaling may regulate a plethora of genes, the dysregulation of Notch signaling often promotes tumor formation (4).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between the Notch signaling pathway and non‑coding RNAs in gastrointestinal cancers (Review)

2017

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Abstract. The Notch signaling pathway is one of the main signaling pathways that mediates direct contact between cells, and is essential for normal development. It regulates various cellular processes, including cell proliferation, apoptosis, migration, invasion, angiogenesis and metastasis. It additionally serves an important function in tumor progression. Non-coding RNAs mainly include small microRNAs, long non-coding RNAs and circular RNAs. At present, a large body of literature supports the biological significance of non-coding RNAs in tumor progression. It is also becoming increasingly evident that cross-talk exists between Notch signaling and non-coding RNAs. The present review summarizes the current knowledge of Notch-mediated gastrointestinal cancer cell processes, and the effect of the crosstalk between the three major types of non-coding RNAs and the Notch signaling pathway on the fate of gastrointestinal cancer cells.

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Notch signaling: An emerging therapeutic target for cancer treatment

Cited by 338 publications

References 89 publications

Intramembrane proteases as drug targets

Intramembrane proteases as drug targets

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Crosstalk between the Notch signaling pathway and non‑coding RNAs in gastrointestinal cancers (Review)

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