Disabling the Nuclear Translocalization of RelA/NF-κB by a Small Molecule Inhibits Triple-Negative Breast Cancer Growth

References

• KeenanTE, TolaneySM. Role of immunotherapy in triple-negative breast cancer. J Natl Compr Canc Netw. 2020;18(4):479–489. doi:10.6004/jnccn.2020.755432259782
   PubMed Web of Science ®Google Scholar
• WaksAG, WinerEP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300. doi:10.1001/jama.2018.1932330667505
   PubMed Web of Science ®Google Scholar
• CaoY, KarinM. NF-kappaB in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 2003;8(2):215–223. doi:10.1023/A:102590500893414635796
   PubMed Web of Science ®Google Scholar
• HeiserLM, SadanandamA, KuoWL, et al. Subtype and pathway specific responses to anticancer compounds in breast cancer. Proc Natl Acad Sci U S A. 2012;109(8):2724–2729. doi:10.1073/pnas.101885410822003129
   PubMed Web of Science ®Google Scholar
• SubbaramaiahK, HoweLR, BhardwajP, et al. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res. 2011;4(3):329–346. doi:10.1158/1940-6207.CAPR-10-0381
   PubMed Web of Science ®Google Scholar
• EgusquiaguirreSP, YehJE, WalkerSR, LiuS, FrankDA. The STAT3 target gene TNFRSF1A modulates the NF-kappaB pathway in breast cancer cells. Neoplasia (New York, NY). 2018;20(5):489–498. doi:10.1016/j.neo.2018.03.004
   Web of Science ®Google Scholar
• LiHH, ZhuH, LiuLS, et al. Tumour necrosis factor-alpha gene polymorphism is associated with metastasis in patients with triple negative breast cancer. Sci Rep. 2015;5:10244. doi:10.1038/srep1024426165253
   PubMed Web of Science ®Google Scholar
• WeeZN, YatimSM, KohlbauerVK, et al. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel. Nat Commun. 2015;6:8746. doi:10.1038/ncomms974626503059
   PubMed Web of Science ®Google Scholar
• WangW, NagSA, ZhangR. Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr Med Chem. 2015;22(2):264–289. doi:10.2174/092986732166614110612431525386819
   PubMed Web of Science ®Google Scholar
• KanzakiH, MukhopadhyaNK, CuiX, RamanujanVK, MuraliR. Trastuzumab-resistant luminal b breast cancer cells show basal-like cell growth features through NF-kappaB-activation. Monoclon Antib Immunodiagn Immunother. 2016;35(1):1–11. doi:10.1089/mab.2015.005626871511
   PubMedGoogle Scholar
• Oliveras-FerrarosC, Vazquez-MartinA, Martin-CastilloB, et al. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin). Int J Oncol. 2010;37(3):669–678. doi:10.3892/ijo_0000071620664936
   PubMed Web of Science ®Google Scholar
• NakshatriH, Bhat-NakshatriP, MartinDA, GouletRJ Jr, SledgeGW Jr. Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol. 1997;17(7):3629–3639. doi:10.1128/MCB.17.7.36299199297
   PubMed Web of Science ®Google Scholar
• YamaguchiN, ItoT, AzumaS, et al. Constitutive activation of nuclear factor-κB is preferentially involved in the proliferation of basal-like subtype breast cancer cell lines. Cancer Sci. 2009;100(9):1668–1674. doi:10.1111/j.1349-7006.2009.01228.x19538528
   PubMed Web of Science ®Google Scholar
• BaldwinAS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. doi:10.1146/annurev.immunol.14.1.6498717528
   PubMed Web of Science ®Google Scholar
• KarinM, DelhaseM. The IκB kinase (IKK) and NF-κB: key elements of proinflammatory signalling. Semin Immunol. 2000;12(1):85–98. doi:10.1006/smim.2000.021010723801
   PubMed Web of Science ®Google Scholar
• KimJY, JungHH, AhnS, et al. The relationship between nuclear factor (NF)-kappaB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment. Sci Rep. 2016;6:31804. doi:10.1038/srep3180427545642
   PubMed Web of Science ®Google Scholar
• UmezawaK. Inhibition of tumor growth by NF-kappaB inhibitors. Cancer Sci. 2006;97(10):990–995. doi:10.1111/j.1349-7006.2006.00285.x16925581
   PubMed Web of Science ®Google Scholar
• LinY, UkajiT, KoideN, UmezawaK. Inhibition of late and early phases of cancer metastasis by the NF-κB inhibitor DHMEQ derived from microbial bioactive metabolite epoxyquinomicin: a review. Int J Mol Sci. 2018;19(3):729. doi:10.3390/ijms19030729
   Web of Science ®Google Scholar
• NetanelyD, AvrahamA, Ben-BaruchA, EvronE, ShamirR. Expression and methylation patterns partition luminal-A breast tumors into distinct prognostic subgroups. Breast Cancer Res. 2016;18(1):74. doi:10.1186/s13058-016-0724-227386846
   PubMed Web of Science ®Google Scholar
• LoveMI, HuberW, AndersS. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi:10.1186/s13059-014-0550-825516281
   PubMed Web of Science ®Google Scholar
• Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289–300.
   Web of Science ®Google Scholar
• MuraliR, ChengX, BerezovA, et al. Disabling TNF receptor signaling by induced conformational perturbation of tryptophan-107. Proc Natl Acad Sci U S A. 2005;102(31):10970–10975. doi:10.1073/pnas.050430110216043718
   PubMed Web of Science ®Google Scholar
• BerezovA, CaiZ, FreudenbergJA, et al. Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin. Oncogene. 2012;31(15):1938–1948. doi:10.1038/onc.2011.37721892210
   PubMed Web of Science ®Google Scholar
• ChenY-Q, GhoshS, GhoshG. A novel DNA recognition mode by the NF-κB p65 homodimer. Nat Struct Biol. 1998;5(1):67–73. doi:10.1038/nsb0198-679437432
   PubMedGoogle Scholar
• JacobsMD, HarrisonSC. Structure of an IκBα/NF-κB complex. Cell. 1998;95(6):749–758. doi:10.1016/S0092-8674(00)81698-09865693
   PubMed Web of Science ®Google Scholar
• ChenFE, HuangD-B, ChenY-Q, GhoshG. Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature. 1998;391(6665):410–413. doi:10.1038/349569450761
   PubMed Web of Science ®Google Scholar
• MorinA, EisenbraunB, KeyJ, et al. Collaboration gets the most out of software. eLife. 2013;2:e01456. doi:10.7554/eLife.0145624040512
   PubMed Web of Science ®Google Scholar
• PrattMA, TibboE, RobertsonSJ, et al. The canonical NF-kappaB pathway is required for formation of luminal mammary neoplasias and is activated in the mammary progenitor population. Oncogene. 2009;28(30):2710–2722. doi:10.1038/onc.2009.13119483731
   PubMed Web of Science ®Google Scholar
• ShostakK, ChariotA. NF-kappaB, stem cells and breast cancer: the links get stronger. Breast Cancer Res. 2011;13(4):214. doi:10.1186/bcr288621867572
   PubMed Web of Science ®Google Scholar
• JonesRL, RojoF, A’HernR, et al. Nuclear NF-kappaB/p65 expression and response to neoadjuvant chemotherapy in breast cancer. J Clin Pathol. 2011;64(2):130–135. doi:10.1136/jcp.2010.08296621148141
   PubMed Web of Science ®Google Scholar
• WangL, KangF, LiJ, ZhangJ, ShanB. Overexpression of p65 attenuates celecoxib-induced cell death in MDA-MB-231 human breast cancer cell line. Cancer Cell Int. 2013;13(1):14. doi:10.1186/1475-2867-13-1423402310
   PubMed Web of Science ®Google Scholar
• JubbH, HiguerueloAP, WinterA, BlundellTL. Structural biology and drug discovery for protein-protein interactions. Trends Pharmacol Sci. 2012;33(5):241–248. doi:10.1016/j.tips.2012.03.00622503442
   PubMed Web of Science ®Google Scholar
• HartmanZC, PoageGM, den HollanderP, et al. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Res. 2013;73(11):3470–3480. doi:10.1158/0008-5472.CAN-12-4524-T23633491
   PubMed Web of Science ®Google Scholar
• LeeST, LiZ, WuZ, et al. Context-specific regulation of NF-kappaB target gene expression by EZH2 in breast cancers. Mol Cell. 2011;43(5):798–810. doi:10.1016/j.molcel.2011.08.01121884980
   PubMed Web of Science ®Google Scholar
• LiS, KendallSE, RaicesR, et al. TWIST1 associates with NF-kappaB subunit RELA via carboxyl-terminal WR domain to promote cell autonomous invasion through IL8 production. BMC Biol. 2012;10:73. doi:10.1186/1741-7007-10-7322891766
   PubMed Web of Science ®Google Scholar
• ParkB-W, ZhangH-T, WuC, et al. Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo. Nat Biotechnol. 2000;18(2):194–198. doi:10.1038/7265110657127
   PubMed Web of Science ®Google Scholar
• GuptaSC, SundaramC, ReuterS, AggarwalBB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta. 2010;1799(10–12):775–787. doi:10.1016/j.bbagrm.2010.05.00420493977
   PubMed Web of Science ®Google Scholar
• BaudV, KarinM. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 2009;8(1):33–40. doi:10.1038/nrd278119116625
   PubMed Web of Science ®Google Scholar
• UmezawaK. Possible role of peritoneal NF-κB in peripheral inflammation and cancer: lessons from the inhibitor DHMEQ. Biomed Pharmacother. 2011;65(4):252–259. doi:10.1016/j.biopha.2011.02.00321723080
   PubMed Web of Science ®Google Scholar
• MuraliR, GreeneMI, Inventors; (The Trustees of the University of Pennsylvania, USA). assignee. Cavity-induced allosteric modification of intermolecular interactions and methods of identifying compounds that effect them. US patent 99-US15062 2000001349. 19990701. 2000.
   Google Scholar
• ChenX, KandasamyK, SrivastavaRK. Differential roles of RelA (p65) and c-Rel subunits of nuclear factor kappa B in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res. 2003;63(5):1059–1066.12615723
   PubMed Web of Science ®Google Scholar
• JacqueE, BillotK, AuthierH, BordereauxD, BaudV. RelB inhibits cell proliferation and tumor growth through p53 transcriptional activation. Oncogene. 2013;32(21):2661–2669. doi:10.1038/onc.2012.28222777360
   PubMed Web of Science ®Google Scholar
• DingH, GangalumPR, GalstyanA, et al. HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug. Nanomedicine. 2017;13(2):631–639. doi:10.1016/j.nano.2016.07.01327520726
   PubMed Web of Science ®Google Scholar
• LevineDH, GhoroghchianPP, FreudenbergJ, et al. Polymersomes: a new multi-functional tool for cancer diagnosis and therapy. Methods. 2008;46(1):25–32. doi:10.1016/j.ymeth.2008.05.00618572025
   PubMed Web of Science ®Google Scholar
• GuillemardV, NedevHN, BerezovA, MuraliR, SaragoviHU. HER2-mediated internalization of a targeted prodrug cytotoxic conjugate is dependent on the valency of the targeting ligand. DNA Cell Biol. 2005;24(6):350–358. doi:10.1089/dna.2005.24.35115941387
   PubMed Web of Science ®Google Scholar
• DeLanoWLThe PyMOL Molecular Graphics System. Palo Alto, CA, USA: DeLando Scientific LLC; 2007. Available from:http://www.pymol.org. Accessed 617, 2021.
   Google Scholar