Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism

Somasundaram, Veena; Basudhar, Debashree; Bharadwaj, Gaurav; No, Jae Hong; Ridnour, Lisa A.; Cheng, Robert; Fujita, Mayumi; Thomas, Douglas D.; Anderson, Stephen; McVicar, Daniel W.; Wink, David A.

doi:10.1089/ars.2018.7527

Cited by 148 publications

(103 citation statements)

References 180 publications

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“…It is notably balanced by pH, temperature, UV-vis irradiations, RSNO micro-environment (influencing its pK a ), chemical nature of RSNO, and presence of reactive compounds such as metal ions ( 254 , 255 ). The dysregulation of NO flux in the tumor micro-environment has also been found to modulate the redox signaling pathways during cancer progression ( 256 ), which might consequently influence RSNOs reactivity. Several compounds are known to react with S -nitrosothiols such as phosphine derivatives, sulfenic acids, and a large variety of nucleophiles.…”

Section: Reactivity Of S -Nitrosothiolsmentioning

confidence: 99%

Computational Structural Biology of S-nitrosylation of Cancer Targets

et al. 2018

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Nitric oxide (NO) plays an essential role in redox signaling in normal and pathological cellular conditions. In particular, it is well known to react in vivo with cysteines by the so-called S-nitrosylation reaction. S-nitrosylation is a selective and reversible post-translational modification that exerts a myriad of different effects, such as the modulation of protein conformation, activity, stability, and biological interaction networks. We have appreciated, over the last years, the role of S-nitrosylation in normal and disease conditions. In this context, structural and computational studies can help to dissect the complex and multifaceted role of this redox post-translational modification. In this review article, we summarized the current state-of-the-art on the mechanism of S-nitrosylation, along with the structural and computational studies that have helped to unveil its effects and biological roles. We also discussed the need to move new steps forward especially in the direction of employing computational structural biology to address the molecular and atomistic details of S-nitrosylation. Indeed, this redox modification has been so far an underappreciated redox post-translational modification by the computational biochemistry community. In our review, we primarily focus on S-nitrosylated proteins that are attractive cancer targets due to the emerging relevance of this redox modification in a cancer setting.

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Section: Reactivity Of S -Nitrosothiolsmentioning

confidence: 99%

Computational Structural Biology of S-nitrosylation of Cancer Targets

et al. 2018

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“…ROS are involved in the hypersensitive response (HR) as well as elicitor signal transduction system ( Allen et al, 2004 ; Hu et al, 2018 ; Jones and Dangl, 2006 ). ROS have been associated with the accumulation of plant secondary metabolites and are ultimately required for enhancing plant immunity reactions ( Asai et al, 2008 ; Somasundaram et al, 2018 ; Zhao et al, 2005 ). The second stage in the activation concerning defence response occurs within few hours of elicitor ingestion.…”

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confidence: 99%

A Novel Protein Elicitor PeBL2, from Brevibacillus laterosporus A60, Induces Systemic Resistance against Botrytis cinerea in Tobacco Plant

et al. 2019

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“…Indo-treated 4T1 disks contained fewer cells than control disks, mirroring effects of the anti-inflammatories in tumors ( Supplementary Fig. 10) 12,13 . These results show that anti-inflammatory compounds modulate cellular phenotypes along the hypoxic gradient, which demonstrates the utility of the 4T1-REEC system for understanding treatment mechanisms in conjunction with hypoxia in the TME.…”

Section: Resultsmentioning

confidence: 86%

“…Nos2 produces nitric oxide (NO), a key regulator of cancer processes 12 , from L-arginine and is upregulated by stabilized HIF1α in response to hypoxia and nutrient deprivation 13 (Supplemental Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

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Flaherty

Somasundaram

et al. 2020

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The tumor microenvironment (TME) is multi-cellular, spatially heterogenous, and contains cell-generated gradients of soluble molecules. Current cell-based model systems lack this complexity or are difficult to interrogate microscopically. We present a 2D live-cell chamber that approximates the TME and demonstrate that breast cancer cells and macrophages generate hypoxic and nutrient gradients, self-organize, and have spatially varying phenotypes along the gradients, leading to new insights into tumorigenesis.

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Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism

Abstract: Understanding the source of NO and its spaciotemporal profile within the tumor microenvironment could help improve efficacy of cancer immunotherapies by improving tumor infiltration of immune cells for better tumor clearance. Antioxid. Redox Signal. 00, 000-000.

Cited by 148 publications

References 180 publications

Computational Structural Biology of S-nitrosylation of Cancer Targets

Computational Structural Biology of S-nitrosylation of Cancer Targets

A Novel Protein Elicitor PeBL2, from Brevibacillus laterosporus A60, Induces Systemic Resistance against Botrytis cinerea in Tobacco Plant

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

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