Display options
Cite
Provance OK, Geanes ES, Lui AJ, et al. Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression. Cancer Lett. 2021;514:12-29doi: 10.1016/j.canlet.2021.05.006.
Provance, O. K., Geanes, E. S., Lui, A. J., Roy, A., Holloran, S. M., Gunewardena, S., Hagan, C. R., Weir, S., & Lewis-Wambi, J. (2021). Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression. Cancer letters, 51412-29. https://doi.org/10.1016/j.canlet.2021.05.006
Provance, Olivia K, et al. "Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression." Cancer letters vol. 514 (2021): 12-29. doi: https://doi.org/10.1016/j.canlet.2021.05.006
Provance OK, Geanes ES, Lui AJ, Roy A, Holloran SM, Gunewardena S, Hagan CR, Weir S, Lewis-Wambi J. Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression. Cancer Lett. 2021 Aug 28;514:12-29. doi: 10.1016/j.canlet.2021.05.006. Epub 2021 May 20. PMID: 34022283; PMCID: PMC8221017.
Copy Download .nbib Format: NLM
Share it on

Cancer Lett. 2021 Aug 28;514:12-29. doi: 10.1016/j.canlet.2021.05.006. Epub 2021 May 20.

Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression.

Cancer letters

Olivia K Provance, Eric S Geanes, Asona J Lui, Anuradha Roy, Sean M Holloran, Sumedha Gunewardena, Christy R Hagan, Scott Weir, Joan Lewis-Wambi

Affiliations

  1. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
  2. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
  3. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; High Throughput Screening Laboratory, University of Kansas, Lawrence, KS, 66049, USA.
  4. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Biochemistry, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
  5. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
  6. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Biochemistry, University of Kansas Medical Center, Kansas City, KS, 66160, USA; The University of Kansas Cancer Center, Kansas City, KS, 66160, USA.
  7. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; The University of Kansas Cancer Center, Kansas City, KS, 66160, USA; The Institute for Advancing Medical Innovation, Kansas City, KS, 66160, USA.
  8. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; The University of Kansas Cancer Center, Kansas City, KS, 66160, USA. Electronic address: [email protected].

PMID: 34022283 PMCID: PMC8221017 DOI: 10.1016/j.canlet.2021.05.006

Abstract

Overexpression of interferon induced transmembrane protein-1 (IFITM1) enhances tumor progression in multiple cancers, but its role in triple-negative breast cancer (TNBC) is unknown. Here, we explore the functional significance and regulation of IFITM1 in TNBC and strategies to target its expression. Immunohistochemistry staining of a tissue microarray demonstrates that IFITM1 is overexpressed in TNBC samples which is confirmed by TCGA analysis. Targeting IFITM1 by siRNA or CRISPR/Cas9 in TNBC cell lines significantly inhibits proliferation, colony formation, and wound healing in vitro. Orthotopic mammary fat pad and mammary intraductal studies reveal that loss of IFITM1 reduces TNBC tumor growth and invasion in vivo. RNA-seq analysis of IFITM1/KO cells reveals significant downregulation of several genes involved in proliferation, migration, and invasion and functional studies identified NF-κB as an important downstream target of IFITM1. Notably, siRNA knockdown of p65 reduces IFITM1 expression and a drug-repurposing screen of FDA approved compounds identified parthenolide, an NFκB inhibitor, as a cytotoxic agent for TNBC and an inhibitor of IFITM1 in vitro and in vivo. Overall, our findings suggest that targeting IFITM1 by suppressing interferon-alpha/NFκB signaling represents a novel therapeutic strategy for TNBC treatment.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords: IFITM1; Interferon; NF-kappaB; Parthenolide; TNBC

References

  1. EMBO J. 2013 Oct 16;32(20):2751-63 - PubMed
  2. Mediators Inflamm. 2010;2010:821940 - PubMed
  3. Pharmaceuticals (Basel). 2020 Aug 14;13(8): - PubMed
  4. N Engl J Med. 2010 Nov 11;363(20):1938-48 - PubMed
  5. Breast Cancer Res. 2019 May 6;21(1):59 - PubMed
  6. Lancet. 2014 Jul 12;384(9938):164-72 - PubMed
  7. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):3906-3911 - PubMed
  8. Nat Prod Rep. 2020 Apr 1;37(4):541-565 - PubMed
  9. Cancer Lett. 2017 Jul 28;399:29-43 - PubMed
  10. Lancet. 2017 Jun 17;389(10087):2430-2442 - PubMed
  11. Breast Cancer Res. 2009;11(5):R66 - PubMed
  12. Breast Cancer Res Treat. 2012 Feb;131(3):765-75 - PubMed
  13. Genome Biol. 2007;8(9):R191 - PubMed
  14. Int J Cancer. 2019 Apr 15;144(8):2020-2032 - PubMed
  15. J Clin Invest. 2019 Apr 1;129(4):1785-1800 - PubMed
  16. Cancer Control. 2010 Jul;17(3):173-6 - PubMed
  17. Cell Death Dis. 2016 Apr 14;7:e2194 - PubMed
  18. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18490-5 - PubMed
  19. Sci Rep. 2019 Feb 7;9(1):1538 - PubMed
  20. Breast Cancer Res Treat. 2017 Jan;161(2):279-287 - PubMed
  21. Cancer Sci. 2018 Oct;109(10):3115-3128 - PubMed
  22. Stem Cell Res Ther. 2020 Jan 7;11(1):16 - PubMed
  23. Neoplasia. 2007 Feb;9(2):166-80 - PubMed
  24. Cell Death Dis. 2013 Oct 31;4:e891 - PubMed
  25. Nat Rev Drug Discov. 2019 Jan;18(1):41-58 - PubMed
  26. Cancer Res. 2017 May 1;77(9):2213-2221 - PubMed
  27. Chem Biol. 2001 Aug;8(8):759-66 - PubMed
  28. Tissue Antigens. 2004 Nov;64(5):533-42 - PubMed
  29. Neoplasia. 2017 Aug;19(8):649-658 - PubMed
  30. Breast Cancer Res Treat. 2010 Oct;123(3):725-31 - PubMed
  31. Annu Rev Immunol. 2005;23:307-36 - PubMed
  32. Hepatology. 2013 Feb;57(2):461-9 - PubMed
  33. Am J Pathol. 2012 Jul;181(1):43-52 - PubMed
  34. Oncol Lett. 2016 Jan;11(1):500-504 - PubMed
  35. Breast. 2014 Oct;23(5):538-45 - PubMed
  36. J Clin Invest. 1997 Dec 15;100(12):2952-60 - PubMed
  37. Biochem Soc Trans. 2017 Apr 15;45(2):531-535 - PubMed
  38. J Natl Cancer Inst. 2005 Dec 7;97(23):1746-59 - PubMed
  39. Clin Cancer Res. 2008 Oct 1;14(19):6097-105 - PubMed
  40. Mol Cancer Res. 2019 May;17(5):1180-1194 - PubMed
  41. Cell Rep. 2015 Jul 14;12(2):300-12 - PubMed
  42. J Interferon Cytokine Res. 2011 Jul;31(7):553-9 - PubMed
  43. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8656-61 - PubMed
  44. Cancer Lett. 2015 Nov 1;368(1):135-143 - PubMed
  45. Oncol Rep. 2014 May;31(5):2139-46 - PubMed
  46. Molecules. 2018 Jun 19;23(6): - PubMed
  47. J Biol Chem. 2001 Apr 27;276(17):13756-61 - PubMed
  48. Cell Chem Biol. 2019 Jul 18;26(7):1027-1035.e22 - PubMed
  49. Neoplasia. 2004 Jan-Feb;6(1):1-6 - PubMed
  50. Breast Cancer Res. 2016 Feb 20;18(1):25 - PubMed
  51. Oncotarget. 2016 Dec 27;7(52):86039-86050 - PubMed
  52. Cancer Res Treat. 2019 Apr;51(2):576-592 - PubMed
  53. Nucleic Acids Res. 2020 Jan 24;48(2):589-604 - PubMed
  54. J Interferon Cytokine Res. 2011 Jan;31(1):183-97 - PubMed
  55. J Clin Invest. 2011 Jul;121(7):2750-67 - PubMed
  56. BMC Genomics. 2015 Apr 17;16:307 - PubMed
  57. Clin Cancer Res. 2012 Jun 1;18(11):3015-21 - PubMed
  58. Cell Commun Signal. 2020 Aug 17;18(1):128 - PubMed

Publication Types

Grant support