Notch signaling and non-small cell lung cancer (Review)

Zou, Bin; Zhou, Xueliang; Lai, Songqing; Liu, Jichun

doi:10.3892/ol.2018.7738

Cited by 36 publications

(35 citation statements)

References 68 publications

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“…inhibiting Notch signaling pathway can inhibit lung tumor cell apoptosis. Overexpression of Notch1 and Notch3 protein molecules and increased lymph node metastasis in NSCLC patients lead to shortened patient survival time [49]. Our research shows that 3 proteins in cluster3 of the core targets are related to Notch signaling pathway.…”

Section: Discussionmentioning

confidence: 65%

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Gong

Wei

et al. 2020

Preprint

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Background: Shenlian Capsule is a Chinese medicine compound approved by the China Food and Drug Administration (CFDA) for the treatment of advanced non-small cell lung cancer(NSCLC). However, due to its complex constituents, cause its effective active compounds and main action mechanisms for treating diseases are still not fully clear. The purpose of this work is to explore the active ingredients and mechanisms of Shenlian Capsule treatment NSCLC through a system pharmacological approach. Methods: First, a database of Shenlian Capsule chemical composition was constructed by retrieving Chinese herbal medicine data. Absorption, distribution, metabolism and excretion (ADME) methods were used to screen potential active compounds. Predict active compound targets with a large-scale molecular network target prediction technology. Clustering of active compounds obtained through cluster analysis by MECODE plug-in, each cluster obtains the main pathways through enrichment analysis method. To get all targets related to survival in NSCLC, the survival related targets were intersected with the compounds target (C-T) network to get the survival related targets for Shenlian Capsule. Finally, a batch molecular docking technique was used to verify the effect of active compounds of Shenlian Capsule on survival-related targets.Results: The Shenlian Capsule C-T network was constructed with 117 potential compounds and 47 targets. Treatment of NSCLC with Shenlian Capsule through enrichment analysis may involve multiple pathways such as anti-inflammatory, immune regulation, regulation of cell cycle, apoptosis, antiviral, cell hypoxia, angiogenesis and so on. Shenlian Capsule has eight survival-related genes in non-small cell lung adenocarcinoma (LUAD) and two survival-related genes in non-small cell squamous cell lung carcinoma (LUSC). It is known through molecular docking that the active compound has lower energy after conformation with survival-related genes, and has lower binding energy and stable binding.Conclusion: In this study, the potential compounds of active compounds in Shenlian Capsule were first predicted using network pharmacology technology. Through the enrichment analysis, the main pathways of the role of Shenlian Capsule were outcropped. Secondly, by combining bioinformatics and network pharmacology, Shenlian Capsule can be regulated to target survival-related targets. Finally, the molecular docking technique shows the relationship between active compounds and survival-related targets after docking. This work provided a scientific basis for the clinical role of Shenlian Capsule in the treatment of NSCLC, provided a research basis for further clarifying the active ingredients and mechanism of Shenlian Capsule in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 65%

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Gong

Wei

et al. 2020

Preprint

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“…Lung cancer is classified into two main categories based on histology: small cell lung cancer (SCLC) and non‐small cell lung cancer (NSCLC). Genes related to Notch signaling are frequently mutated or aberrantly expressed in SCLC and NSCLC, although the functions of these gene in oncogenesis are context‐dependent (Zou, Zhou, Lai, & Liu, ). In 2000, Dang TP et al.…”

Section: Notch Signaling In Respiratory Diseasesmentioning

confidence: 99%

“…A number of studies have reported that Notch signaling is involved in tumorigenesis, yet its detailed biological roles in NSCLC remain elusive (Zou et al., ). The necessity of Notch1 for Kras‐induced lung adenocarcinoma in transgenic mice was demonstrated by the Notch‐mediated suppression of p53‐mediated apoptosis (Licciulli et al., ; Xu et al., ).…”

Section: Notch Signaling In Respiratory Diseasesmentioning

confidence: 99%

Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease

Kiyokawa

Morimoto

2019

Dev Growth Differ

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The respiratory system has ideal tissue structure and cell types for efficient gas exchange to intake oxygen and release carbon dioxide. This complex system develops through orchestrated intercellular signaling among various cell types, such as club, ciliated, basal, neuroendocrine, AT1, AT2, endothelial, and smooth muscle cells. Notch signaling is a highly conserved cell–cell signaling pathway ideally suited for very short‐range cellular communication because Notch signals are transmitted by direct contact with an adjacent cell. Enthusiastic efforts by Notch researchers over the last two decades have led to the identification of critical roles of this signaling pathway during development, homeostasis, and regeneration of the respiratory system. The dysregulation of Notch signaling results in a wide range of respiratory diseases such as pulmonary artery hypertension (PAH), chronic obstructive pulmonary disease (COPD), interstitial pulmonary fibrosis (IPF), and lung cancer. Thus, a deep understanding of the biological functions of Notch signaling will help identify novel treatment targets in various respiratory diseases.

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“…The plethora of ligands regulating NOTCH receptors have been extensively studied in different tumour types for their onco-regulatory effects [75][76][77]. Depending on the biological microenvironment, the activation of NOTCH signaling seems to have a dual role, showing an oncogenic effects in certain tissues (i.e.…”

Section: Structure Of Notch Receptors and Notch Signaling Pathwaymentioning

confidence: 99%

Updates on the Role of Molecular Alterations and NOTCH Signaling in the Development of Neuroendocrine Neoplasms

Arx¹,

Capozzi²,

López‐Jiménez³

et al. 2019

Preprint

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Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

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Notch signaling and non-small cell lung cancer (Review)

Cited by 36 publications

References 68 publications

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease

Updates on the Role of Molecular Alterations and NOTCH Signaling in the Development of Neuroendocrine Neoplasms

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