Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Cancer metastasis occurs due to the ability of the tumour to evade immune recognition and response by altering the major histocompatibility complex class I (MHC class I). A comprehensive understanding of the MHC class I alteration in breast cancer metastasis is vital for the rational design and improvement of immunotherapies for advanced cancer. In this study, we associate it with the elevation of ‘neonatal’ Nav1.5 (nNav1.5) mRNA expression in the aggressive type of human breast cancer cells. Using real-time PCR, lower expression of TAP1 (by − 4.83-fold), which is a part of the MHC class I antigen processing machinery (APM) pathway component, in contrast to the greater expression of nNav1.5 (by 3.76-fold), along with other metastatic markers, MMP1 (by 57.48-fold) and fibronectin (by 2.88-fold) in aggressive human breast cancer cell line, MDA-MB-231 were obtained. Subsequent knockdown of nNav1.5 (by 52.6%) in MDA-MB-231 via siRNA-SCN5A resulted in downregulation of another metastatic marker, fibronectin (by 52.9%) but importantly, rescued MHC class I expression (by 347% or 3.47-fold). Furthermore, the siRNA-SCN5A transfected cells failed to form a unified spheroid and incapable of efficiently invading the surrounding invasion matrix. In summary, the influence of nNav1.5 in regulating MHC class I mRNA expression to allow for breast cancer invasion is demonstrated, supporting the potential of nNav1.5 as an immunotherapy target to overcome tumour immune evasion thus preventing metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Adair SJ and Hogan KT 2009 Treatment of ovarian cancer cell lines with 5-aza-2’-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules. Cancer Immunol. Immunother. 58 589–601

    Article  CAS  PubMed  Google Scholar 

  • Amith SR, Wilkinson JM and Fliegel L 2016a KR-33028, a potent inhibitor of the Na(+)/H(+) exchanger NHE1, suppresses metastatic potential of triple-negative breast cancer cells. Biochem. Pharmacol 118 31–39

    Article  CAS  PubMed  Google Scholar 

  • Amith SR, Wilkinson JM and Fliegel L 2016b Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells. Oncotarget 7 21091–21113

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson P, Aptsiauri N, Ruiz-Cabello F and Garrido F 2021 HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy. Cell. Mol. Immunol. 18 556–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balanis N, Wendt MK, Schiemann BJ, Wang Z, Schiemann WP, et al. 2013 Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway. J. Biol. Chem. 288 17954–17967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baskaran JP, Weldy A, Guarin J, Munoz G, Shpilker PH, et al. 2020 Cell shape, and not 2D migration, predicts extracellular matrix-driven 3D cell invasion in breast cancer. APL Bioeng. 4 026105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boström P, Söderström M, Vahlberg T, Söderström K-O, Roberts PJ, et al. 2011 MMP-1 expression has an independent prognostic value in breast cancer. BMC Cancer 11 348

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brackenbury WJ 2012 Voltage-gated sodium channels and metastatic disease. Channels 6 352–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brackenbury WJ, Chioni AM, Diss JK and Djamgoz MB 2007 The neonatal splice variant of Nav1.5 potentiates in vitro invasive behaviour of MDA-MB-231 human breast cancer cells. Breast Cancer Res. Treat. 101 149–160

    Article  PubMed  Google Scholar 

  • Brea EJ, Oh CY, Manchado E, Budhu S, Gejman RS, et al. 2016 Kinase regulation of human MHC Class I molecule expression on cancer cells. Cancer Immunol. Res. 4 936–947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brisson L, Gillet L, Calaghan S, Besson P, Le Guennec JY, et al. 2011 NaV1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H+ efflux in caveolae. Oncogene 30 2070–2076

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Fernandez MA, Sierra A, Garrido A, Herruzo A, et al. 1996 High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum. Immunol. 50 127–134

    Article  CAS  PubMed  Google Scholar 

  • Campbell TM, Main MJ and Fitzgerald EM 2013 Functional expression of the voltage-gated Na+-channel Nav1. 7 is necessary for EGF-mediated invasion in human non-small cell lung cancer cells. J. Cell Sci. 126 4939–4949

    CAS  PubMed  Google Scholar 

  • Carrithers MD, Chatterjee G, Carrithers LM, Offoha R, Iheagwara U, et al. 2009 Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. J. Biol. Chem. 284 8114–8126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charoen KM, Fallica B, Colson YL, Zaman MH and Grinstaff MW 2014 Embedded multicellular spheroids as a biomimetic 3D cancer model for evaluating drug and drug-device combinations. Biomaterials 35 2264–2271

    Article  CAS  PubMed  Google Scholar 

  • Chen DS and Mellman I 2017 Elements of cancer immunity and the cancer–immune set point. Nature 541 321–330

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Wong C, Vosburgh E, Levine AJ, Foran DJ, et al. 2014 High-throughput image analysis of tumor spheroids: a user-friendly software application to measure the size of spheroids automatically and accurately. J. vis. Exp.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chioni A-M, Fraser SP, Pani F, Foran P, Wilkin GP, et al. 2005 A novel polyclonal antibody specific for the Nav1. 5 voltage-gated Na+ channel ‘neonatal’splice form. J. Neurosci. Methods 147 88–98

    Article  CAS  PubMed  Google Scholar 

  • Choi JY, Jang YS, Min SY and Song JY 2011 Overexpression of MMP-9 and HIF-1α in breast cancer cells under hypoxic conditions. J. Breast Cancer 14 88–95

    Article  PubMed  PubMed Central  Google Scholar 

  • Dai X, Cheng H, Bai Z and Li J 2017 Breast cancer cell line classification and its relevance with breast tumor subtyping. J. Cancer 8 3131

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Delarue M, Montel F, Vignjevic D, Prost J, Joanny J-F, et al. 2014 Compressive stress inhibits proliferation in tumor spheroids through a volume limitation. Biophys. J. 107 1821–1828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denac H, Mevissen M and Scholtysik G 2000 Structure, function and pharmacology of voltage-gated sodium channels. Naunyn-Schmiedeberg’s Arch. Pharmacol. 362 453–479

    Article  CAS  Google Scholar 

  • Dewadas HD, Kamarulzaman NS, Yaacob NS, Che Has AT and Mokhtar NF 2019 The role of HIF-1α, CBP and p300 in the regulation of Nav1.5 expression in breast cancer cells. Gene Rep. 16 100405

    Article  Google Scholar 

  • Dhatchinamoorthy K, Colbert JD and Rock KL 2021 Cancer immune evasion through loss of MHC Class I antigen presentation. Front. Immunol

    Article  PubMed  PubMed Central  Google Scholar 

  • Djordjevic B and Lange CS 2006 Cell-cell interactions in spheroids maintained in suspension. Acta Oncologica 45 412–420

    Article  CAS  PubMed  Google Scholar 

  • Dolfini E, Roncoroni L, Dogliotti E, Sala G, Erba E, et al. 2007 Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids concomitant with ceramide accumulation. Cancer Lett. 249 143–147

    Article  CAS  PubMed  Google Scholar 

  • Fraser SP, Diss JK, Chioni A-M, Mycielska ME, Pan H, et al. 2005 Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin. Cancer Res. 11 5381–5389

    Article  CAS  PubMed  Google Scholar 

  • Froehlich K, Haeger J-D, Heger J, Pastuschek J, Photini SM, et al. 2016 Generation of multicellular breast cancer tumor spheroids: comparison of different protocols. J. Mammary Gland Biol. Neoplasia 21 89–98

    Article  PubMed  Google Scholar 

  • Garcia-Lora A, Algarra I and Garrido F 2003 MHC class I antigens, immune surveillance, and tumor immune escape. J. Cell. Physiol. 195 346–355

    Article  CAS  PubMed  Google Scholar 

  • Garrido F and Aptsiauri N 2019 Cancer immune escape: MHC expression in primary tumours versus metastases. Immunology 158 255–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido F, Aptsiauri N, Doorduijn EM, Garcia Lora AM and van Hall T 2016 The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr. Opin. Immunol. 39 44–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D and Weinberg RA 2011 Hallmarks of cancer: the next generation. Cell 144 646–674

    Article  CAS  PubMed  Google Scholar 

  • House CD, Vaske CJ, Schwartz AM, Obias V, Frank B, et al. 2010 Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res. 70 6957–6967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • House CD, Wang B-D, Ceniccola K, Williams R, Simaan M, et al. 2015 Voltage-gated Na+ channel activity increases colon cancer transcriptional activity and invasion via persistent MAPK signaling. Sci. Rep. 5 11541

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang Z, Yu P and Tang J 2020 Characterization of triple-negative breast cancer MDA-MB-231 cell spheroid model. Oncol. Targets Ther. 13 5395–5405

    Article  CAS  Google Scholar 

  • Ivanov DP and Grabowska AM 2017 Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D. Sci. Rep. 7 41160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivanov DP, Parker TL, Walker DA, Alexander C, Ashford MB, et al. 2014 Multiplexing spheroid volume, resazurin and acid phosphatase viability assays for high-throughput screening of tumour spheroids and stem cell neurospheres. PLoS ONE 9 e103817

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ivascu A and Kubbies M 2006 Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J. Biomol. Screen. 11 922–932

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Wang X, Zhang C, Xue L and Yang L 2020 Expression and clinical significance of MAPK and EGFR in triple-negative breast cancer. Oncol. Lett. 19 1842–1848

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kamarulzaman NS, Dewadas HD, Leow CY, Yaacob NS and Mokhtar NF 2017 The role of REST and HDAC2 in epigenetic dysregulation of Nav1.5 and nNav1.5 expression in breast cancer. Cancer Cell Int. 17 74 

  • Kaneko K, Ishigami S, Kijima Y, Funasako Y, Hirata M, et al. 2011 Clinical implication of HLA class I expression in breast cancer. BMC Cancer 11 454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, et al. 2003 A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3 537–549

    Article  CAS  PubMed  Google Scholar 

  • Kim R, Emi M and Tanabe K 2007 Cancer immunoediting from immune surveillance to immune escape. Immunology 121 1–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim TY, Kofron CM, King ME, Markes AR, Okundaye AO, et al. 2018 Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts. PLoS ONE 13 e0196714

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lagies S, Schlimpert M, Neumann S, Wäldin A, Kammerer B, et al. 2020 Cells grown in three-dimensional spheroids mirror in vivo metabolic response of epithelial cells. Commun. Biol. 3 246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert AW, Pattabiraman DR and Weinberg RA 2017 Emerging Biological principles of metastasis. Cell 168 670–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lankat-Buttgereit B and TampÉ R 2003 The transporter associated with antigen processing (TAP): a peptide transport and loading complex essential for cellular immune response; in ABC proteins (eds) Holland IB, Kuchler K and Higgins CF (Cambridge: Academic Press London) 533–550

    Chapter  Google Scholar 

  • Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, et al. 2016 Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy. J. Am. Chem. Soc. 138 13967–13974

    Article  CAS  PubMed  Google Scholar 

  • Li S, Zhang J, Yang H, Wu C, Dang X et al. 2015 Copper depletion inhibits CoCl 2-induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition. Sci. Rep. 5 12410

  • Ling A, Löfgren-Burström A, Larsson P, Li X, Wikberg ML, et al. 2017 TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. Oncoimmunology 6 e1356143

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu H, Kato Y, Erzinger SA, Kiriakova GM, Qian Y, et al. 2012 The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer 12 583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu C, Ma Z, Cheng X, Wu H, Tuo B, et al. 2020 Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer. Cancer Cell Int. 20 377

    Article  PubMed  PubMed Central  Google Scholar 

  • Luo Q, Wu T, Wu W, Chen G, Luo X, et al. 2020 The functional role of voltage-gated sodium channel Nav1.5 in metastatic breast cancer. Front. Pharmacol. 11 1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma G, Pan Y, Zhou C, Sun R, Bai J, et al. 2015 Mitogen-activated protein kinase phosphatase 1 is involved in tamoxifen resistance in MCF7 cells. Oncol. Rep. 34 2423–2430

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, López-Nevot MA, Cabrera T, Salinero J and Garrido F 2002 Multiple mechanisms generate HLA class I altered phenotypes in laryngeal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Cancer Immunol. Immunother. 51 389–396

    Article  CAS  PubMed  Google Scholar 

  • Marincola FM, Jaffee EM, Hicklin DJ and Ferrone S 1999 Escape of human solid tumors from T–cell recognition: Molecular mechanisms and functional significance. Adv. Immunol. 74 181–273

    Article  Google Scholar 

  • McGranahan N, Rosenthal R, Hiley CT, Rowan AJ, Watkins TBK, et al. 2017 Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171 1259-1271.e1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mittler F, Obeïd P, Rulina AV, Haguet V, Gidrol X, et al. 2017 High-content monitoring of drug effects in a 3D spheroid model. Front. Oncol. 7 293

    Article  PubMed  PubMed Central  Google Scholar 

  • Nagelkerke A, Bussink J, Sweep FC and Span PN 2013 Generation of multicellular tumor spheroids of breast cancer cells: how to go three-dimensional. Anal. Biochem. 437 17–19

    Article  CAS  PubMed  Google Scholar 

  • Neumann H, Schmidt H, Cavalie A, Jenne D and Wekerle H 1997 Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-γ and tumor necrosis factor (TNF)-α. J. Exp. Med. 185 305–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Praest P, Luteijn RD, Brak-Boer IGJ, Lanfermeijer J, Hoelen H, et al. 2018 The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins. Mol. Immunol. 101 55–64

    Article  CAS  PubMed  Google Scholar 

  • Radisky ES and Radisky DC 2010 Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J. Mammary Gland Biol. Neoplasia 15 201–212

    Article  PubMed  PubMed Central  Google Scholar 

  • Rajaratinam H, Rasudin NS, Al Astani TAD, Mokhtar NF, Yahya MM, et al. 2021 Breast cancer therapy affects the expression of antineonatal Nav1.5 antibodies in the serum of patients with breast cancer. Oncol. Lett. 21 108

    Article  CAS  PubMed  Google Scholar 

  • Ramos GdO, Bernardi L, Lauxen I, Sant’Ana Filho M, Horwitz AR, et al. 2016 Fibronectin modulates cell adhesion and signaling to promote single cell migration of highly invasive oral squamous cell carcinoma. PLoS ONE 11 e0151338

    Article  PubMed Central  CAS  Google Scholar 

  • Rezaei N and Keshavarz-Fathi M 2018 Vaccines for cancer immunotherapy: an evidence-based review on current status and future perspectives (Cambridge: Academic Press)

    Google Scholar 

  • Roger S, Besson P and Le Guennec J-Y 2003 Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochim. Biophys. Acta Biomembr. 1616 107–111

    Article  CAS  Google Scholar 

  • Savio Galimberti E, Gollob M and Darbar D 2012 Voltage-gated sodium channels: biophysics, pharmacology, and related channelopathies. Front. Pharmacol. 3 124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmittgen TD and Livak KJ 2008 Analyzing real-time PCR data by the comparative C T method. Nat. Protocols 3 1101

    Article  CAS  PubMed  Google Scholar 

  • Schroeter A, Walzik S, Blechschmidt S, Haufe V, Benndorf K, et al. 2010 Structure and function of splice variants of the cardiac voltage-gated sodium channel Nav1.5. J. Mol. Cell. Cardiol. 49 16–24

    Article  CAS  PubMed  Google Scholar 

  • Silva GBRFd, Silva TGA, Duarte RA, Neto NL, Carrara HHA et al. 2013 Expression of the classical and nonclassical HLA molecules in breast cancer. Int. J. Breast Cancer 2013 250435

  • Turajlic S, Sottoriva A, Graham T and Swanton C 2019 Resolving genetic heterogeneity in cancer. Nat. Rev. Genet. 20 404–416

    Article  CAS  PubMed  Google Scholar 

  • Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, et al. 2007 Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res. 35 W71–W74

    Article  PubMed  PubMed Central  Google Scholar 

  • Vitale M, Rezzani R, Rodella L, Zauli G, Grigolato P, et al. 1998 HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res. 58 737–742

    CAS  PubMed  Google Scholar 

  • Walpita D and Hay E 2002 Studying actin-dependent processes in tissue culture. Nat. Rev. Mol. Cell Biol. 3 137

    Article  CAS  PubMed  Google Scholar 

  • Wan S, Pestka S, Jubin RG, Lyu YL, Tsai YC, et al. 2012 Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS ONE 7 e32542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang B, Niu D, Lai L and Ren EC 2013 p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1. Nat. Commun. 4 2359–2359

  • Wang J, Ni Z, Duan Z, Wang G and Li F 2014 Altered expression of hypoxia-inducible factor-1α (HIF-1α) and its regulatory genes in gastric cancer tissues. PLoS ONE 9 e99835

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang JP and Hielscher A 2017 Fibronectin: how its aberrant expression in tumors may improve therapeutic targeting. J. Cancer 8 674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang QM, Lv L, Tang Y, Zhang L and Wang LF 2019 MMP-1 is overexpressed in triple-negative breast cancer tissues and the knockdown of MMP-1 expression inhibits tumor cell malignant behaviors in vitro. Oncol. Lett. 17 1732–1740

    CAS  PubMed  Google Scholar 

  • Welsh J 2013 Animal models for studying prevention and treatment of breast cancer; in Animal Models for the Study of Human Disease (Conn PM Ed) (Academic Press Boston) pp 997–1018

  • Wright LE, Ottewell PD, Rucci N, Peyruchaud O, Pagnotti GM, et al. 2016 Murine models of breast cancer bone metastasis. Bonekey Rep. 5 804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X-X, Yue GG-L, Dong J-R, Lam CW-K, Wong C-K, et al. 2018 Actein inhibits the proliferation and adhesion of human breast cancer cells and suppresses migration in vivo. Front. Pharmacol. 9 1466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia J, Huang N, Huang H, Sun L, Dong S, et al. 2016 Voltage-gated sodium channel Nav 1.7 promotes gastric cancer progression through MACC1-mediated upregulation of NHE1. Int. J. Cancer 139 2553–2569

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Zhang F, Wang A, Wang C, Cao Y et al. 2016 Tumor necrosis factor-like weak inducer of apoptosis promotes hepatic stellate cells migration via canonical NF-κB/MMP9 pathway. PLoS ONE 11 e0167658

  • Yamaci RF, Fraser SP, Battaloglu E, Kaya H, Erguler K, et al. 2017 Neonatal Nav1. 5 protein expression in normal adult human tissues and breast cancer. Pathol. Res. Practice 213 900–907

    Article  CAS  Google Scholar 

  • Yang M, Kozminski DJ, Wold LA, Modak R, Calhoun JD, et al. 2012 Therapeutic potential for phenytoin: targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res. Treat. 134 603–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, et al. 2012 Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 13 134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamora AE, Crawford JC and Thomas PG 2018 Hitting the target: how T Cells detect and eliminate tumors. J. Immunol. 200 392–399

    Article  CAS  PubMed  Google Scholar 

  • Zanotelli VR, Leutenegger M, Lun X-K, Georgi F, de Souza N, et al. 2020 A quantitative analysis of the interplay of environment, neighborhood, and cell state in 3D spheroids. Mol. Syst. Biol. 16 e9798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Chen Y, Liu Z and Lai R 2018 ERK is a negative feedback regulator for IFN-γ/STAT1 signaling by promoting STAT1 ubiquitination. BMC Cancer 18 613

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou F 2009 Molecular mechanisms of IFN-gamma to up-regulate MHC class I antigen processing and presentation. Int. Rev. Immunol. 28 239–260

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The highest gratitude is extended to the personnel of the Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia for technical assistance. We would also like to acknowledge the Ministry of Education, Malaysia for the research financial support – The Fundamental Research Grant Scheme (203/CIPPM/6171212) and Yayasan Khazanah for the postgraduate financial support.

Author information

Authors and Affiliations

  1. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Ahmad Hafiz Murtadha, Irfan Irsyad Mohd Azahar, Nur Aishah Sharudin & Noor Fatmawati Mokhtar

  2. Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Ahmad Tarmizi Che Has

Authors
  1. Ahmad Hafiz Murtadha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irfan Irsyad Mohd Azahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nur Aishah Sharudin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmad Tarmizi Che Has
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noor Fatmawati Mokhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noor Fatmawati Mokhtar.

Additional information

Communicated by Dipankar Nandi.

Corresponding editor: Dipankar Nandi

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 61 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murtadha, A.H., Azahar, I.I.M., Sharudin, N.A. et al. Influence of nNav1.5 on MHC class I expression in breast cancer. J Biosci 46, 70 (2021). https://doi.org/10.1007/s12038-021-00196-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12038-021-00196-w

Keywords

Search

Navigation