NF-κB Signaling in Tumor Pathways Focusing on Breast and Ovarian Cancer

Overview

Journal Oncol Rev

Specialty Oncology

Date 2022 Dec 19

PMID 36531159

Authors

Monika Devanaboyina

Jasskiran Kaur

Emma Whiteley

Leslie Lin

Katelyn Einloth

Susan Morand

Laura Stanbery

Danae Hamouda

John Nemunaitis

Affiliations

Soon will be listed here.

Abstract

Immune disorders and cancer share a common pathway involving NF-κb signaling. Through involvement with GM-CSF, NF-κB can contribute to proliferation and activation of T- and B- cells as well as immune cell migration to sites of inflammation. In breast cancer, this signaling pathway has been linked to resistance with endocrine and chemotherapies. Similarly, in ovarian cancer, NF-κB influences angiogenesis and inflammation pathways. Further, BRCA1 signaling common to both breast and ovarian cancer also has the capability to induce NF-κB activity. Immunotherapy involving NF-κB can also be implemented to combat chemoresistance. The complex signaling pathways of NF-κB can be harnessed for developing cancer therapeutics to promote immunotherapy for improving patient outcomes.

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References

Pan Y, Wang S, Su B, Zhou F, Xu T, Zhang R . Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression. Oncogene. 2016; 36(8):1069-1079. PMC: 5311075. DOI: 10.1038/onc.2016.271. View

Yang C, Gonzalez-Angulo A, Reuben J, Booser D, Pusztai L, Krishnamurthy S . Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Ann Oncol. 2006; 17(5):813-7. DOI: 10.1093/annonc/mdj131. View

Kalaitzidis D, Gilmore T . Transcription factor cross-talk: the estrogen receptor and NF-kappaB. Trends Endocrinol Metab. 2005; 16(2):46-52. DOI: 10.1016/j.tem.2005.01.004. View

Tiffon C, Adams J, van der Fits L, Wen S, Townsend P, Ganesan A . The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL-10 expression in cutaneous T-cell lymphoma cells. Br J Pharmacol. 2011; 162(7):1590-602. PMC: 3057296. DOI: 10.1111/j.1476-5381.2010.01188.x. View

Sakumoto R, Okuda K . Possible actions of tumor necrosis factor-alpha in ovarian function. J Reprod Dev. 2004; 50(1):39-46. DOI: 10.1262/jrd.50.39. View

Hayden M, Ghosh S . NF-κB in immunobiology. Cell Res. 2011; 21(2):223-44. PMC: 3193440. DOI: 10.1038/cr.2011.13. View

Bubici C, Papa S, Dean K, Franzoso G . Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene. 2006; 25(51):6731-48. DOI: 10.1038/sj.onc.1209936. View

Mirzaei H, Masoudifar A, Sahebkar A, Zare N, Nahand J, Rashidi B . MicroRNA: A novel target of curcumin in cancer therapy. J Cell Physiol. 2017; 233(4):3004-3015. DOI: 10.1002/jcp.26055. View

Li F, Sethi G . Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta. 2010; 1805(2):167-80. DOI: 10.1016/j.bbcan.2010.01.002. View

10.

Mitrakas L, Gravas S, Papandreou C, Koukoulis G, Karasavvidou F, Dimakopoulos G . Primary High-Grade Non-Muscle-Invasive Bladder Cancer: High NFκB Expression in Tumor Specimens Distinguishes Patients Who are at Risk for Disease Progression. Pathol Oncol Res. 2017; 25(1):225-231. DOI: 10.1007/s12253-017-0340-1. View

11.

Tsubaki M, Komai M, Fujimoto S, Itoh T, Imano M, Sakamoto K . Activation of NF-κB by the RANKL/RANK system up-regulates snail and twist expressions and induces epithelial-to-mesenchymal transition in mammary tumor cell lines. J Exp Clin Cancer Res. 2013; 32:62. PMC: 3847095. DOI: 10.1186/1756-9966-32-62. View

12.

Tergaonkar V, Bottero V, Ikawa M, Li Q, Verma I . IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB activity and implications for cancer therapy. Mol Cell Biol. 2003; 23(22):8070-83. PMC: 262380. DOI: 10.1128/MCB.23.22.8070-8083.2003. View

13.

Infante M, Fabi A, Cognetti F, Gorini S, Caprio M, Fabbri A . RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. J Exp Clin Cancer Res. 2019; 38(1):12. PMC: 6325760. DOI: 10.1186/s13046-018-1001-2. View

14.

Kiechl S, Schramek D, Widschwendter M, Fourkala E, Zaikin A, Jones A . Aberrant regulation of RANKL/OPG in women at high risk of developing breast cancer. Oncotarget. 2016; 8(3):3811-3825. PMC: 5354797. DOI: 10.18632/oncotarget.14013. View

15.

Israel A . The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol. 2010; 2(3):a000158. PMC: 2829958. DOI: 10.1101/cshperspect.a000158. View

16.

Harte M, Gorski J, Savage K, Purcell J, Barros E, Burn P . NF-κB is a critical mediator of BRCA1-induced chemoresistance. Oncogene. 2013; 33(6):713-723. PMC: 3917825. DOI: 10.1038/onc.2013.10. View

17.

Imai D, Yoshizumi T, Okano S, Itoh S, Ikegami T, Harada N . IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer. J Surg Res. 2019; 240:115-123. DOI: 10.1016/j.jss.2019.02.038. View

18.

Turner J, Kashyap T, Dawson J, Gomez J, Bauer A, Grant S . XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IκBα and overcomes acquired proteasome inhibitor resistance in human multiple myeloma. Oncotarget. 2016; 7(48):78896-78909. PMC: 5340237. DOI: 10.18632/oncotarget.12969. View

19.

Lee S, Seo S, Kim B, Kim C, Lee J, Kang J . IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells. J Dermatol Sci. 2005; 40(2):95-103. DOI: 10.1016/j.jdermsci.2005.06.008. View

20.

Nagarajan R, Chen F, Li W, Vig E, Harrington M, Nakshatri H . Repression of transforming-growth-factor-beta-mediated transcription by nuclear factor kappaB. Biochem J. 2000; 348 Pt 3:591-6. PMC: 1221102. View