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IFNs-signaling effects on lung cancer: an up-to-date pathways-specific review

Clinical and Experimental Medicine volume 17, pages 281–289 (2017)Cite this article

Abstract

IFNs have found important applications in clinical medicine, including the treatment of lung malignancies. The biological effect of the IFN-receptor signaling is regulated essentially by three factors: the expression profile of the IFN itself, the profile of the receptor, and the expression of target genes. IFNs initiate their signaling by binding to specific receptors. The activated IFNs can directly induce gene transcription and/or multiple downstream signaling that both induce diverse cellular responses including the cell cycle arrest and the apoptosis in tumor cells. We provided evidence that IFN-γ enhances the pro cell death effects of Fas/CD95 in human neoplastic alveolar epithelial cell line, A549. We also found that p27 protein plays a pivotal role in the inducing cell death of IFNγ-CH-11-treated A549 cells, since it is involved in the Ras/Raf signaling pathway. This article discusses recent insights into these possible additional functions of IFNs in lung cancer treatment.

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Abbreviations

NK:

Natural killer cells

PI3-K:

Phosphatidylinositol-3-kinases

FAK:

Focal adhesion kinase

MapKapK:

MAP kinase-activated protein kinase

MTOR:

Mammalian target of rapamycin

FRAP1:

FK506-binding protein 12-rapamycin-associated protein 1

PIK3CA:

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

RAF:

Rapidly accelerated fibrosarcoma

CBL:

Casitas B-lineage lymphoma

I-TAC:

Inducible T cell alpha chemoattractant

References

  1. Pestka S, Langer JA, Zoon KC, Samuel CE. Interferons and their actions. Annu Rev Biochem. 1987;56:727–77.

    Article  CAS  PubMed  Google Scholar 

  2. Pfeffer LM, Dinarello CA, Herberman RB, et al. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons. Cancer Res. 1998;58(12):2489–99.

    CAS  PubMed  Google Scholar 

  3. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–64.

    Article  CAS  PubMed  Google Scholar 

  4. Uddin S, Majchrzak B, Woodson J, et al. Activation of the p38 mitogen-activated protein kinase by type I interferons. J Biol Chem. 1999;274(42):30127–31.

    Article  CAS  PubMed  Google Scholar 

  5. Brierley MM, Fish EN. Review: IFN-alpha/beta receptor interactions to biologic outcomes: understanding the circuitry. J Interferon Cytokine Res. 2002;22(8):835–45.

    Article  CAS  PubMed  Google Scholar 

  6. Parmar S, Platanias LC. Interferons: mechanisms of action and clinical applications. Curr Opin Oncol. 2003;15(6):431–9.

    Article  CAS  PubMed  Google Scholar 

  7. Galani V, Tatsaki E, Bai M, et al. The role of apoptosis in the pathophysiology of Acute Respiratory Distress Syndrome (ARDS): an up-to-date cell-specific review. Pathol Res Pract. 2010;206(3):145–50.

    Article  CAS  PubMed  Google Scholar 

  8. Pestka S. Interferon standards and general abbreviations. Methods Enzymol. 1986;119:14–23.

    Article  CAS  PubMed  Google Scholar 

  9. Pestka S. The human interferon alpha species and hybrid proteins. Semin Oncol. 1997;24:S9-4–-17.

    Google Scholar 

  10. Kotenko SV, Gallagher G, Baurin VV, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003;4(1):69–77.

    Article  CAS  PubMed  Google Scholar 

  11. de Weerd NA, Nguyen T. The interferons and their receptors—distribution and regulation. Immunol Cell Biol. 2002;90(5):483–91.

    Article  Google Scholar 

  12. Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 2013;45(2):164–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Borden EC, Sen GC, Uze G, et al. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007;6:975–90.

    Article  CAS  PubMed  Google Scholar 

  14. De Weerd NA, Samarajiwa SA, Hertzog PJ. Type I interferon receptors: biochemistry and biological functions. J Biol Chem. 2007;282:20053–7.

    Article  PubMed  Google Scholar 

  15. Colamonici OR, Domanski P, Krolewski JJ, et al. Interferon alpha (IFN alpha) signaling in cells expressing the variant form of the type I IFN receptor. J Biol Chem. 1994;2269(8):5660–5.

    Google Scholar 

  16. Novick D, Cohen B, Rubinstein M. The humaninterferon cxlp receptor: characterization and molecular cloning. Cell. 1994;77:391–400.

    Article  CAS  PubMed  Google Scholar 

  17. Domanski P, Witte M, Kellum M, et al. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem. 1995;270(37):21606–11.

    Article  CAS  PubMed  Google Scholar 

  18. Bach EA, Aguet M, Schreiber RD. The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol. 1997;15:563–91.

    Article  CAS  PubMed  Google Scholar 

  19. Bernabei P, Coccia EM, Rigamonti L, et al. Interferon-gamma receptor 2 expression as the deciding factor in human T, B, and myeloid cell proliferation or death. J Leukoc Biol. 2001;70(6):950–60.

    CAS  PubMed  Google Scholar 

  20. Donnelly RP, Kotenko SV. Interferon-lambda: a new addition to an old family. J Interferon Cytokine Res. 2010;30(8):555–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sommereyns C, Paul S, Staeheli P, Michiels T. IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog. 2008;4(3):e1000017.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mordstein M, Neugebauer E, Ditt V, et al. Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J Virol. 2010;84(11):5670–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dickensheets H, Sheikh F, Park O, Gao B, Donnelly RP. Interferon-lambda (IFN-lambda) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes. J Leukoc Biol. 2013;93(3):377–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Uddin S, Platanias LC. Mechanisms of type-I interferon signal transduction. J Biochem Mol Biol. 2004;37(6):635–41.

    CAS  PubMed  Google Scholar 

  25. Domanski P, Fish E, Nadeau OW, et al. A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jakl and is sufficient to activate the Jak-stat pathway and induce an antiviral state. J Biol Chem. 1997;272(42):26388–93.

    Article  CAS  PubMed  Google Scholar 

  26. Darnell JE. STATs and gene regulation. Science. 1997;277(5332):1630–5.

    Article  CAS  PubMed  Google Scholar 

  27. Platanias LC, Fish EN. Signaling pathways activated by interferons. Exp Hematol. 1999;27:1583–92.

    Article  CAS  PubMed  Google Scholar 

  28. Darnell JE. Studies of IFN-induced transcriptional activation uncover the Jak-Stat pathway. J Interferon Cytokine Res. 1998;18:549–54.

    Article  CAS  PubMed  Google Scholar 

  29. Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749–95.

    Article  CAS  PubMed  Google Scholar 

  30. Luszczek W, Cheriyath V, Mekhail TM, Borden EC. Combinations of DNA methyltransferase and histone deacetylase inhibitors induce DNA damage in small cell lung cancer cells: correlation of resistance with IFN-stimulated gene expression. Mol Cancer Ther. 2010;9:2309–21.

    Article  CAS  PubMed  Google Scholar 

  31. Decker T, Kovarik P. Serine phosphorylation of STATs. Oncogene. 2000;19:2628–37.

    Article  CAS  PubMed  Google Scholar 

  32. Uddin S, Sassano A, Deb DK, et al. Protein kinase C-delta (PKC-delta) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem. 2002;277:14408–16.

    Article  CAS  PubMed  Google Scholar 

  33. Deb DK, Sassano A, Lekmine F, et al. Activation of protein kinase C delta by IFN-gamma. J Immunol. 2003;171:267–73.

    Article  CAS  PubMed  Google Scholar 

  34. Clark AS, West KA, Blumberg PM, Dennis PA. Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance. Cancer Res. 2003;63(4):780–6.

    CAS  PubMed  Google Scholar 

  35. Lasfar A, Lewis-Antes A, Smirnov SV, et al. Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res. 2006;66:4468–77.

    Article  CAS  PubMed  Google Scholar 

  36. Sato A, Ohtsuki M, Hata M, Kobayashi E, Murakami M. Antitumor activity of IFN-lambda in murine tumor models. J Immunol. 2006;176:7686–94.

    Article  CAS  PubMed  Google Scholar 

  37. Ernst M, Jenkins BJ. Acquiring signalling specificity from the cytokine receptor gp130. Trends Genet. 2004;20(1):23–32.

    Article  CAS  PubMed  Google Scholar 

  38. Galani V, Constantopoulos S, Manda-Stachouli C, et al. Additional proteins in BAL fluid of Metsovites environmentally exposed to asbestos: More evidence of “protection” against neoplasia? Chest. 2002;121(1):273–8.

    Article  PubMed  Google Scholar 

  39. Dauer DJ, Ferraro B, Song L, et al. Stat3 regulates genes common to both wound healing and cancer. Oncogene. 2005;24:3397–408.

    Article  CAS  PubMed  Google Scholar 

  40. Xie TX, Huang FJ, Aldape KD, et al. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res. 2006;66:3188–96.

    Article  CAS  PubMed  Google Scholar 

  41. Li WC, Ye SL, Sun RX, et al. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 2006;12:7140–8.

    Article  CAS  PubMed  Google Scholar 

  42. Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. The role of STATs in lung carcinogenesis: an emerging target for novel therapeutics. J Mol Med. 2007;85:427–36.

    Article  CAS  PubMed  Google Scholar 

  43. Song MM, Shuai K. The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem. 1998;273:35056–62.

    Article  CAS  PubMed  Google Scholar 

  44. Kabir NN, Sun J, Rönnstrand L, Kazi JU. SOCS6 is a selective suppressor of receptor tyrosine kinase signaling. Tumour Biol. 2014;35(11):10581–9.

    Article  CAS  PubMed  Google Scholar 

  45. Lowell CA. Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk. Cold Spring Harb Perspect Biol. 2011;3(3):a002352.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Uddin S, Sher DA, Alsayed Y, et al. Interaction of p59fyn with interferon-activated Jak kinases. Biochem Biophys Res Commun. 1997;235:83–8.

    Article  CAS  PubMed  Google Scholar 

  47. Uddin S, Grumbach IM, Yi T, Colamonici OR, Platanias LC. Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells. Br J Haematol. 1998;101:446–9.

    Article  CAS  PubMed  Google Scholar 

  48. Byers LA, Sen B, Saigal B, et al. Reciprocal regulation of c-Src and STAT3 in non-small cell lung cancer. Clin Cancer Res. 2009;15(22):6852–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang XHF, Wang Q, Gerald W, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell. 2009;16(1):67–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Carretero J, Shimamura T, Rikova K, et al. Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. Cancer Cell. 2010;17(6):547–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Li Y, Srivastava KK, Platanias LC. Mechanisms of type I interferon signaling in normal and malignant cells. Arch Immunol Ther Exp (Warsz). 2004;52(3):156–63.

    CAS  Google Scholar 

  52. White MF, Kahn CR. The insulin signaling system. J Biol Chem. 1994;269(1):1–4.

    CAS  PubMed  Google Scholar 

  53. Uddin S, Yenush L, Sun XJ, et al. Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3′-kinase. J Biol Chem. 1995;270(27):15938–41.

    Article  CAS  PubMed  Google Scholar 

  54. Platanias LC, Uddin S, Yetter A, Sun XJ, White MF. The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2. J Biol Chem. 1996;271(1):278–82.

    Article  CAS  PubMed  Google Scholar 

  55. Kaur S, Katsoulidis E, Platanias LC. Akt and mRNA translation by interferons. Cell Cycle. 2008;7:2112–6.

    Article  CAS  PubMed  Google Scholar 

  56. Chou MM, Blenis J. The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling. Curr Opin Cell Biol. 1995;7:806–14.

    Article  CAS  PubMed  Google Scholar 

  57. Thyrell L, Hjortsberg L, Arulampalam V, et al. Interferon alpha-induced apoptosis in tumor cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway. J Biol Chem. 2004;279:24152–62.

    Article  CAS  PubMed  Google Scholar 

  58. Schmeisser H, Fey SB, Horowitz J, et al. Type I interferons induce autophagy in certain human cancer cell lines. Autophagy. 2013;9(5):683–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Platanias LC, Sweet ME. Interferon alpha induces rapid tyrosine phosphorylation of the vav proto-oncogene product in hematopoietic cells. J Biol Chem. 1994;269(5):3143–6.

    CAS  PubMed  Google Scholar 

  60. Adam L, Bandyopadhyay D, Kumar R. Interferon alpha signaling promotes nucleus-to-cytoplasmic redistribution of p95Vav, and formation of a multisubunit complex involving Vav, Ku80, and Tyk2. Biochem Biophys Res Commun. 2000;267:692–6.

    Article  CAS  PubMed  Google Scholar 

  61. Micouin A, Wietzerbin J, Steunou V, Martyre MC. p95 (vav) associates with the type I interferon (IFN) receptor and contributes to the antiproliferative effect of IFNalpha in megakaryocytic cell lines. Oncogene. 2000;19:387–94.

    Article  CAS  PubMed  Google Scholar 

  62. Uddin S, Lekmine F, Sharma N, et al. The Rac1/p38 mitogen-activated protein kinase pathway is required for interferon alpha-dependent transcriptional activation but not serine phosphorylation of Stat proteins. J Biol Chem. 2000;275:27634–40.

    CAS  PubMed  Google Scholar 

  63. Gastonguay A, Berg T, Hauser AD, et al. The role of Rac1 in the regulation of NF-κB activity, cell proliferation, and cell migration in non-small cell lung carcinoma. Cancer Biol Ther. 2012;13(8):647–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998;95(1):29–39.

    Article  CAS  PubMed  Google Scholar 

  65. Hong TM, Yang PC, Peck K, et al. Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by complementary DNA microarray. Am J Respir Cell Mol Biol. 2000;23(3):355–63.

    Article  CAS  PubMed  Google Scholar 

  66. Marsit CJ, Zheng S, Aldape K, et al. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol. 2005;36(7):768–76.

    Article  CAS  PubMed  Google Scholar 

  67. Chen CL, Chiang TH, Tseng PC, et al. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-gamma. Biochem Biophys Res Commun. 2015;466(3):578–84.

    Article  CAS  PubMed  Google Scholar 

  68. Cui M, Augert A, Rongione M, et al. PTEN is a potent suppressor of small cell lung cancer. Mol Cancer Res. 2014;12(5):654–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ahmad S, Alsayed YM, Druker BJ, Platanias LC. The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J Biol Chem. 1997;272:29991–4.

    Article  CAS  PubMed  Google Scholar 

  70. Fish EN, Uddin S, Korkmaz M, et al. Activation of a CrkL-stat5 signaling complex by type I interferons. J Biol Chem. 1999;274:571–3.

    Article  CAS  PubMed  Google Scholar 

  71. Miller CT, Chen G, Gharib TG, et al. Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas. Oncogene. 2003;22:7950–7.

    Article  PubMed  Google Scholar 

  72. Platanias LC. The p38 mitogen-activated protein kinase pathway and its role in interferon signaling. Pharmacol Ther. 2003;98:129–42.

    Article  CAS  PubMed  Google Scholar 

  73. Greenberg AK, Basu S, Hu J, et al. Selective p38 activation in human non-small cell lung cancer. Am J Respir Cell Mol Biol. 2002;26:558–64.

    Article  CAS  PubMed  Google Scholar 

  74. Whitmarsh AJ, Davis RJ. Role of mitogen activated protein kinase kinase 4 in cancer. Oncogene. 2007;26:3172–84.

    Article  CAS  PubMed  Google Scholar 

  75. Ventura JJ. p38a MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 2007;39:750–8.

    Article  CAS  PubMed  Google Scholar 

  76. David M, Petricoin EI, Benjamin C, et al. Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. Science. 1995;269(5231):1721–3.

    Article  CAS  PubMed  Google Scholar 

  77. Adjei AA. Signal transduction pathway targets for anticancer drug discovery. Curr Pharm Des. 2000;6(4):362–78.

    Article  Google Scholar 

  78. Lorusso PM. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J Clin Oncol. 2005;23:5281–93.

    Article  CAS  PubMed  Google Scholar 

  79. Kastamoulas M, Chondrogiannis G, Kanavaros P, et al. Cytokine effects on cell survival and death of A549 lung carcinoma cells. Cytokine. 2013;61(3):816–25.

    Article  CAS  PubMed  Google Scholar 

  80. Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13(2):95–109.

    Article  CAS  PubMed  Google Scholar 

  81. Hayakawa Y, Takeda K, Yagita H, et al. IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood. 2002;100(5):1728–33.

    CAS  PubMed  Google Scholar 

  82. Liu K, Abrams SI. Coordinate regulation of IFN consensus sequence-binding protein and caspase-1 in the sensitization of human colon carcinoma cells to Fas-mediated apoptosis by IFN-gamma. J Immunol. 2003;170:6329–37.

    Article  CAS  PubMed  Google Scholar 

  83. Vivo C, Lévy F, Pilatte Y, et al. Control of cell cycle progression in human mesothelioma cells treated with gamma interferon. Oncogen. 2001;20:1085–93.

    Article  CAS  Google Scholar 

  84. Chen B, He L, Savell VH, Jenkins JJ, Parham DM. Inhibition of the interferon-gamma/signal transducers and activators of transcription (STAT) pathway by hypermethylation at a STAT-binding site in the p21WAF1 promoter region. Cancer Res. 2000;60(12):3290–8.

    CAS  PubMed  Google Scholar 

  85. Galani V, Chondrogiannis G, Kastamoulas M, et al. TNF-alpha, IL1-beta, IL-13 and IFN-gamma effects on the cell death of the A549 lung carcinoma cells. FEBS J. 2009;276(Suppl 1):310.

    Google Scholar 

  86. Fujie H, Tanaka T, Tagawa M, et al. Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small cell lung cancer. Cancer Sci. 2011;102(11):1977–90.

    Article  CAS  PubMed  Google Scholar 

  87. Li W, Huang X, Liu Z, et al. Type III interferon induces apoptosis in human lung cancer cells. Oncol Rep. 2012;28(3):1117–25.

    CAS  PubMed  Google Scholar 

  88. Tezuka Y, Endo S, Matsui A, et al. Potential anti-tumor effect of IFN-lambda 2 (IL-28A) against human lung cancer cells. Lung Cancer. 2012;78(3):185–92.

    Article  PubMed  Google Scholar 

  89. Iversen TZ, Andersen MH, Svane IM. The targeting of indoleamine 2,3 dioxygenase-mediated immune escape in cancer. Basic Clin Pharmacol Toxicol. 2015;116(1):19–24.

    Article  CAS  PubMed  Google Scholar 

  90. Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncol. 2001;6(1):34–55.

    Article  CAS  Google Scholar 

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    Authors and Affiliations

    1. Department of Anatomy-Histology-Embryology, Faculty of Medicine, University of Ioannina, 45110, Ioannina, Greece

      Vasiliki Galani & Michalis Kastamoulas

    2. Department of Ippokratio Hospital, Thessaloníki, Greece

      Anna Varouktsi

    3. Department of Cancer Biobank Center, University of Ioannina, Ioannina, Greece

      Evangeli Lampri

    4. Department of Forensic Pathology, Faculty of Medicine, University of Ioannina, Ioannina, Greece

      Antigoni Mitselou

    5. Department of Anatomy-Histology-Embryology, Faculty of Medicine, University of Thessaly, Larissa, Greece

      Dimitrios L. Arvanitis

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    1. Vasiliki Galani
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    Vasiliki Galani, Michalis Kastamoulas, Anna Varouktsi, Evangeli Lampri, Antigoni Mitselou and Dimitrios L. Arvanitis have equally contributed to this review.

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    Galani, V., Kastamoulas, M., Varouktsi, A. et al. IFNs-signaling effects on lung cancer: an up-to-date pathways-specific review. Clin Exp Med 17, 281–289 (2017). https://doi.org/10.1007/s10238-016-0432-3

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    Keywords

    • IFNs-receptors
    • IFNs-signaling
    • Profile IFNs
    • Lung cancer

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