Influence of nNav1.5 on MHC class I expression in breast cancer

Murtadha, Ahmad Hafiz; Azahar, Irfan Irsyad Mohd; Sharudin, Nur Aishah; Has, Ahmad Tarmizi Che; Mokhtar, Najat

doi:10.1007/s12038-021-00196-w

Cited by 5 publications

(4 citation statements)

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“…It has previously been suggested that the employment of treatment such as chemotherapy and radiation in breast cancer may stimulate the expression of MHC class I [ 167 ]. Such phenomenon is supported via findings discovered by Murthadha et al [ 168 ], where the downregulation of nNav1.5 in aggressive breast cancer cells positively upregulates the expression of MHC class I. Such upregulation reflects the activation of the antitumour immune response, which is crucial in eliminating oncogenic proteins, including nNav1.5.…”

Section: The Involvement Of Nav15 In the Functionality Of The Immune ...supporting

confidence: 60%

“…In addition to infiltration of TILs, TNBC also possesses a low level of MHC class I proteins which is crucial for the survival of the subtype [ 171 , 172 ]. Since the downregulation of nNav1.5 rescues the expression of MHC class I [ 168 ], we believe that by targeting nNav1.5 using compatible immune checkpoint inhibitors, the progression of TNBC could be suppressed.…”

Section: Reassembling the Triad And Future Perspectivesmentioning

confidence: 99%

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Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

et al. 2022

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Nav1.5 is one of the nine voltage-gated sodium channel-alpha subunit (VGSC-α) family members. The Nav1.5 channel typically carries an inward sodium ion current that depolarises the membrane potential during the upstroke of the cardiac action potential. The neonatal isoform of Nav1.5, nNav1.5, is produced via VGSC-α alternative splicing. nNav1.5 is known to potentiate breast cancer metastasis. Despite their well-known biological functions, the immunological perspectives of these channels are poorly explored. The current review has attempted to summarise the triad between Nav1.5 (nNav1.5), breast cancer, and the immune system. To date, there is no such review available that encompasses these three components as most reviews focus on the molecular and pharmacological prospects of Nav1.5. This review is divided into three major subsections: (1) the review highlights the roles of Nav1.5 and nNav1.5 in potentiating the progression of breast cancer, (2) focuses on the general connection between breast cancer and the immune system, and finally (3) the review emphasises the involvements of Nav1.5 and nNav1.5 in the functionality of the immune system and the immunogenicity. Compared to the other subsections, section three is pretty unexploited; it would be interesting to study this subsection as it completes the triad.

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Section: The Involvement Of Nav15 In the Functionality Of The Immune ...supporting

confidence: 60%

Section: Reassembling the Triad And Future Perspectivesmentioning

confidence: 99%

Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

et al. 2022

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“…The overexpression of voltage-gated sodium channels has been shown to be associated with metastatic behavior in a variety of human cancers, including breast cancer, prostate cancer, lung cancer, colorectal cancer, cervical cancer, lymphoma, and neuroblastoma (131,132). Overexpression of the neonatal isoform of the voltage-gated sodium channel, Nav1.5 (nNav1.5), is associated with aggressive human breast cancer metastasis and patient death (131,133,134). Nav1.5 overexpression increases metastasis and invasiveness of breast cancer cells by altering H+ efflux and promoting epithelial-to-mesenchymal transition and the expression of cysteine cathepsin (132), possibly due to reduced expression of salt-inducible kinase 1 (SIK1) (135).…”

Section: Brugada Syndrome and Cancersmentioning

confidence: 99%

Brugada Syndrome: Warning of a Systemic Condition?

D'Imperio

Monasky

Micaglio

et al. 2021

Front. Cardiovasc. Med.

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Brugada syndrome (BrS) is a hereditary disorder, characterized by a specific electrocardiogram pattern and highly related to an increased risk of sudden cardiac death. BrS has been associated with other cardiac and non-cardiac pathologies, probably because of protein expression shared by the heart and other tissue types. In fact, the most commonly found mutated gene in BrS, SCN5A, is expressed throughout nearly the entire body. Consistent with this, large meals and alcohol consumption can trigger arrhythmic events in patients with BrS, suggesting a role for organs involved in the digestive and metabolic pathways. Ajmaline, a drug used to diagnose BrS, can have side effects on non-cardiac tissues, such as the liver, further supporting the idea of a role for organs involved in the digestive and metabolic pathways in BrS. The BrS electrocardiogram (ECG) sign has been associated with neural, digestive, and metabolic pathways, and potential biomarkers for BrS have been found in the serum or plasma. Here, we review the known associations between BrS and various organ systems, and demonstrate support for the hypothesis that BrS is not only a cardiac disorder, but rather a systemic one that affects virtually the whole body. Any time that the BrS ECG sign is found, it should be considered not a single disease, but rather the final step in any number of pathways that ultimately threaten the patient's life. A multi-omics approach would be appropriate to study this syndrome, including genetics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and glycomics, resulting eventually in a biomarker for BrS and the ability to diagnose this syndrome using a minimally invasive blood test, avoiding the risk associated with ajmaline testing.

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“…This benefits directly for future therapeutic development with better specificity on a single epitope, allowing mass production of diagnostic tools for nNav1.5. As for glutamate, including the fact that nNav1.5 is correlated with metastatic breast cancer and in other cases also shows significance of blocking nNav1.5 on another molecule such as Major Histocompatibility Complex (MHC) Class I [24].…”

Section: Discussionmentioning

confidence: 99%

nNav1.5 expression is associated with glutamate level in breast cancer cells

et al. 2022

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Background Glutamate and voltage-gated sodium channels, both have been the target of intense investigation for its involvement in carcinogenesis and progression of malignant disease. Breast cancer with increased level of glutamate often metastasize to other organs (especially bone), whilst re-expression of ‘neonatal’ Nav1.5, nNav1.5 in breast cancer is known to promote cell invasion in vitro, metastasis in vivo and positive lymph node metastasis in patients. Methods In this study, the role of nNav1.5 in regulating glutamate level in human breast cancer cells was examined using pharmacological approach (VGSCs specific blocker, TTX, glutamate release inhibitor, riluzole and siRNA-nNav1.5). Effect of these agents were evaluated based on endogenous and exogenous glutamate concentration using glutamate fluorometric assay, mRNA expression of nNav1.5 using qPCR and finally, invasion using 3D culture assay. Results Endogenous and exogenous glutamate levels were significantly higher in aggressive human breast cancer cells, MDA-MB-231 cells compared to less aggressive human breast cancer cells, MCF-7 and non-cancerous human breast epithelial cells, MCF-10A. Treatment with TTX to MDA-MB-231 cells resulted in significant reduction of endogenous and exogenous glutamate levels corresponded with significant suppression of cell invasion. Subsequently, downregulation of nNav1.5 gene was observed in TTX-treated cells. Conclusions An interesting link between nNav1.5 expression and glutamate level in aggressive breast cancer cells was detected and requires further investigation.

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Influence of nNav1.5 on MHC class I expression in breast cancer

Cited by 5 publications

References 86 publications

Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

Brugada Syndrome: Warning of a Systemic Condition?

nNav1.5 expression is associated with glutamate level in breast cancer cells

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