Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and Caveolin-1 Upregulation

Chanvorachote, Pithi; Pongrakhananon, Varisa; Chunhacha, Preedakorn

doi:10.1155/2014/941359

Cited by 17 publications

(15 citation statements)

References 29 publications

(48 reference statements)

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“…The mRNAs of NO-treated cells were analyzed with microarrays and bioinformatics approaches to identify potential transcription factors and epigenetics modifiers in comparison to those of un-treated cells. Our results showed that several transcription factors identified as molecular targets of NO play a role in the formation and maintenance of CSC (20) and the aggressive behaviors related with CSCs (17,18,25). These results, along with cell-based analysis, revealed that NO promotes the dedifferentiation of lung cancer by increasing the CSC transcription factors and proteins (21).…”

Section: Discussionsupporting

confidence: 54%

“…Regarding lung cancer, many studies have reported the presence of CSCs in NSCLC and associated them to drug resistance, metastasis, and cancer relapse (36). Moreover, several pieces of evidences have shown that NO can promote the aggressive behavior of cancer for which CSCs are responsible (7,17,18,20,21,25). Herein, we focused on illustrating the molecular profile of the NSCLC exposed to a non-toxic concentration of NO that OR: Odds ratio.…”

Section: Discussionmentioning

confidence: 99%

“…Nitric oxide (NO) donor, dipropylenetriamine (DPTA) NONOate, was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Previous studies showed that DPTA (NO donor) was relatively non-toxic to non-small cell lung cancer cell lines (17,21,25), and the non-toxic concentration for H460 cells were 0-50 μM. In this study, 10×10 4 cells of H460 were seeded overnight and treated with 40 μM of DPTA for 5 days (the freshly prepared DPTA was replace every day).…”

Section: Methodsmentioning

confidence: 95%

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Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide

Maiuthed

Prakhongcheep

Chanvorachote

2020

Cancer Genomics Proteomics

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Background/Aim: Nitric oxide (NO) is recognized as an important biological mediator that exerts several human physiological functions. As its nature is an aqueous soluble gas that can diffuse through cells and tissues, NO can affect cell signaling, the phenotype of cancer and modify surrounding cells. The variety of effects of NO on cancer cell biology has convinced researchers to determine the defined mechanisms of these effects and how to control this mediator for a better understanding as well as for therapeutic gain. Materials and Methods: We used bioinformatics and pharmacological experiments to elucidate the potential regulation and underlying mechanisms of NO in non-small a lung cancer cell model. Results: Using microarrays, we identified a total of 151 NO-regulated genes (80 upregulated genes, 71 down-regulated genes) with a strong statistically significant difference compared to untreated controls. Among these, the genes activated by a factor of more than five times were: DCBLD2,

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 95%

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Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide

Maiuthed

Prakhongcheep

Chanvorachote

2020

Cancer Genomics Proteomics

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“…Production of nitric oxide (NO) via nitric oxide synthase (NOS2) plays a key role in inflammation-dependent head and neck cancer progression [25]. Yet, that production has shown to exert controversial effects on EMT [26, 27]. To explore if a possible link prevailed between NOS2 with EMT in LSCC, we analyzed the profile of association of NOS2 with EMT by IHC.…”

Section: Resultsmentioning

confidence: 99%

Expression Analysis of the Mediators of Epithelial to Mesenchymal Transition and Early Risk Assessment of Therapeutic Failure in Laryngeal Carcinoma

Kariche

Moulaï²,

Sellam

et al. 2019

Journal of Oncology

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Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy which lacks early predictors of prognosis. Here, we hypothesized that expression and prognostic characterization of the critical mediators of epithelial to mesenchymal transition (EMT) may provide key information in this regard. Linear regression and multiple correspondence analyses were performed on immunohistochemical data obtained from 20 invasive tumors. Principal component and unsupervised hierarchical clustering were used to analyze the dataset patterns associating with LSCC metastatic profile. Survival and death risk assessments were performed using Kaplan–Meier and hazard ratio tests. Data mining analysis using CHAID decision tree and logistic regression analysis was applied to define the predictive value of the risk factors of tumor aggressiveness. Our analyses showed, that in invasive LSCC tumors, cells associating with a mesenchymal profile were likely to exhibit enhanced NOS2, TGF-β, and IL-17A expression levels, concomitantly to NF-κB nuclear translocation. IHC data deciphering determined that EMT induction was also linked to the enrichment of the tumors with CD68+ populations and IL-10 signal. Strikingly, dataset cluster analysis showed that these signatures could define distinct patterns of invasive tumors, where NOS2 associated with IL-10 expression, and TGF-β and IL-17A signals associated with MMP-9 activation. Decision tree analysis identified IL-17A as a possible predictor of LSCC aggressiveness. Altogether, our results show that distinct immunological patterns would support the acquisition of EMT features in invasive LSCC and suggest that IL-17A may be useful in the early identification of patients “at-risk” of therapeutic failure.

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“…Cav-1 is known to regulate several cancer cell behaviors, including migration (47), invasion (48), and anoikis resistance (49). Because Cav-1 is up-regulated by NO, we tested whether Cav-1 could be involved in the regulation of lung CSCs.…”

Section: Caveolin-1 Enhances the Degradation Of Oct4 Via Ubiquitinpromentioning

confidence: 99%

Nitric oxide promotes cancer cell dedifferentiation by disrupting an Oct4:caveolin-1 complex: A new regulatory mechanism for cancer stem cell formation

Maiuthed

Bhummaphan

Luanpitpong

et al. 2018

Journal of Biological Chemistry

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Cancer stem cells (CSCs) are unique populations of cells that can self-renew and generate different cancer cell lineages. Although CSCs are believed to be a promising target for novel therapies, the specific mechanisms by which these putative therapeutics could intervene are less clear. Nitric oxide (NO) is a biological mediator frequently up-regulated in tumors and has been linked to cancer aggressiveness. Here, we search for targets of NO that could explain its activity. We find that it directly affects the stability and function of octamer-binding transcription factor 4 (Oct4), known to drive the stemness of lung cancer cells. We demonstrated that NO promotes the CSC-regulatory activity of Oct4 through a mechanism that involves complex formation between Oct4 and the scaffolding protein caveolin-1 (Cav-1). In the absence of NO, Oct4 forms a molecular complex with Cav-1, which promotes the ubiquitin-mediated proteasomal degradation of Oct4. NO promotes Akt-dependent phosphorylation of Cav-1 at tyrosine 14, disrupting the Cav-1:Oct4 complex. Site-directed mutagenesis and computational modeling studies revealed that the hydroxyl moiety at tyrosine 14 of Cav-1 is crucial for its interaction with Oct4. Both removal of the hydroxyl via mutation to phenylalanine and phosphorylation lead to an increase in binding free energy (Δ) between Oct4 and Cav-1, destabilizing the complex. Together, these results unveiled a novel mechanism of CSC regulation through NO-mediated stabilization of Oct4, a key stem cell transcription factor, and point to new opportunities to design CSC-related therapeutics.

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Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and Caveolin-1 Upregulation

Cited by 17 publications

References 29 publications

Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide

Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide

Expression Analysis of the Mediators of Epithelial to Mesenchymal Transition and Early Risk Assessment of Therapeutic Failure in Laryngeal Carcinoma

Nitric oxide promotes cancer cell dedifferentiation by disrupting an Oct4:caveolin-1 complex: A new regulatory mechanism for cancer stem cell formation

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