Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells

Molecular and Cellular Biology

Volumn 34, Issue 16, 2014, Pages 2961-2980

  Zafar, Anjum ^a   Wu, Fan ^a   Hardy, Kristine ^a   Li, Jasmine ^a   Juan Tu, Wen ^a   McCuaig, Robert ^a   Harris, Janelle ^b   Kum Khanna, Kum ^b   Attema, Joanne ^c   Gregory, Philip A ^c   Goodall, Gregory ^c,d   Harrington, Kirsti ^e   Dahlstrom, Jane E ^e,f   Boulding, Tara ^a   Madden, Rebecca ^a   Tan, Abel ^a   Milburn, Peter J ^g   Rao, Sudha ^a  

^a UNIVERSITY OF CANBERRA   (Australia)

^b QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^c Centre for Cancer Biology and Department of Haematology   (Australia)

^d UNIVERSITY OF ADELAIDE   (Australia)

^e CANBERRA HOSPITAL   (Australia)

^f The Australian National University   (Australia)

^g AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CD24 ANTIGEN; HERMES ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN KINASE C THETA; TRANSFORMING GROWTH FACTOR BETA;

5' UNTRANSLATED REGION; ARTICLE; BREAST CANCER; CANCER STEM CELL; CELL DIFFERENTIATION; CHROMATIN; COHORT ANALYSIS; CONTROLLED STUDY; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; GENE CONTROL; GENE EXPRESSION; GENOME ANALYSIS; HUMAN; HUMAN CELL; HUMAN TISSUE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION;

ANTIGENS, CD24; ANTIGENS, CD44; BREAST NEOPLASMS; CELL DIFFERENTIATION; CHROMATIN; CHROMATIN ASSEMBLY AND DISASSEMBLY; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; ISOENZYMES; MCF-7 CELLS; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NEOPLASTIC STEM CELLS; NF-KAPPA B P50 SUBUNIT; PROTEIN KINASE C; RECEPTORS, UROKINASE PLASMINOGEN ACTIVATOR; RNA INTERFERENCE; RNA, MESSENGER; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; SPHEROIDS, CELLULAR; TRANSCRIPTION FACTOR RELA; TRANSFORMING GROWTH FACTOR BETA;

EID: 84904488713     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01693-13     Document Type: Article

References (97)

1. Boyer B, Valles AM, Edme N. 2000. Induction and regulation of epithelial- mesenchymal transitions. Biochem. Pharmacol. 60:1091-1099. http://dx.doi.org/10.1016/S0006-2952(00)00427-5.
2. Huber MA, Kraut N, Beug H. 2005. Molecular requirements for epithelial- mesenchymal transition during tumor progression. Curr. Opin. Cell Biol. 17:548-558. http://dx.doi.org/10.1016/j.ceb.2005.08.001.
3. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. 2008. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704-715. http://dx.doi.org/10.1016/j.cell.2008.03.027.
4. Thiery JP, Acloque H, Huang RY, Nieto MA. 2009. Epithelialmesenchymal transitions in development and disease. Cell 139:871-890. http://dx.doi.org/10.1016/j.cell.2009.11.007.
5. Glinsky GV, Berezovska O, Glinskii AB. 2005. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J. Clin. Invest. 115:1503-1521. http://dx.doi.org/10.1172/JCI23412.
6. Lee CW, Simin K, Liu Q, Plescia J, Guha M, Khan A, Hsieh CC, Altieri DC. 2008. A functional Notch-survivin gene signature in basal breast cancer. Breast Cancer Res. 10:R97. http://dx.doi.org/10.1186/bcr2200.
7. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. 2003. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 100:3983-3988. http://dx.doi.org/10.1073/pnas.0530291100.
8. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS. 2003. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17:1253-1270. http://dx.doi.org/10.1101/gad.1061803.
9. Al-Ejeh F, Smart CE, Morrison BJ, Chenevix-Trench G, Lopez JA, Lakhani SR, Brown MP, Khanna KK. 2011. Breast cancer stem cells: treatment resistance and therapeutic opportunities. Carcinogenesis 32: 650-658. http://dx.doi.org/10.1093/carcin/bgr028.
10. Dean M. 2005. Cancer stem cells: implications for cancer causation and therapy resistance. Discov. Med. 5:278-282.
11. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. 2006. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756-760. http://dx.doi.org/10.1038/nature05236.
12. Diehn M, Clarke MF. 2006. Cancer stem cells and radiotherapy: new insights into tumor radioresistance. J. Natl. Cancer Inst. 98:1755-1757. http://dx.doi.org/10.1093/jnci/djj505.
13. Phillips TM, McBride WH, Pajonk F. 2006. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J. Natl. Cancer Inst. 98:1777-1785. http://dx.doi.org/10.1093/jnci/djj495.
14. Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM. 2007. WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc. Natl. Acad. Sci. U. S. A. 104:618-623. http://dx.doi.org/10.1073/pnas.0606599104.
15. Barski A, Jothi R, Cuddapah S, Cui K, Roh TY, Schones DE, Zhao K. 2009. Chromatin poises miRNA- and protein-coding genes for expression. Genome Res. 19:1742-1751. http://dx.doi.org/10.1101/gr.090951.109.
16. Li B, Carey M, Workman JL. 2007. The role of chromatin during transcription. Cell 128:707-719. http://dx.doi.org/10.1016/j.cell.2007.01.015.
17. Loyola A, Bonaldi T, Roche D, Imhof A, Almouzni G. 2006. PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol. Cell 24:309-316. http://dx.doi.org/10.1016/j.molcel.2006.08.019.
18. Metzger E, Wissmann M, Yin N, Muller JM, Schneider R, Peters AH, Gunther T, Buettner R, Schule R. 2005. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437:436-439.
19. Rao S, Gerondakis S, Woltring D, Shannon MF. 2003. c-Rel is required for chromatin remodeling across the IL-2 gene promoter. J. Immunol. 170:3724-3731. http://dx.doi.org/10.4049/jimmunol.170.7.3724.
20. Rao S, Procko E, Shannon MF. 2001. Chromatin remodeling, measured by a novel real-time polymerase chain reaction assay, across the proximal promoter region of the IL-2 gene. J. Immunol. 167:4494-4503. http://dx.doi.org/10.4049/jimmunol.167.8.4494.
21. Strahl BD, Allis CD. 2000. The language of covalent histone modifications. Nature 403:41-45. http://dx.doi.org/10.1038/47412.
22. Sutcliffe EL, Parish IA, He YQ, Juelich T, Tierney ML, Rangasamy D, Milburn PJ, Parish CR, Tremethick DJ, Rao S. 2009. Dynamic histone variant exchange accompanies gene induction in T cells. Mol. Cell. Biol. 29:1972-1986. http://dx.doi.org/10.1128/MCB.01590-08.
23. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, Schones DE, Peng W, Sun HW, Paul WE, O'Shea JJ, Zhao K. 2009. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30:155-167. http://dx.doi.org/10.1016/j.immuni.2008.12.009.
24. Chow CW, Davis RJ. 2006. Proteins kinases: chromatin-associated enzymes? Cell 127:887-890. http://dx.doi.org/10.1016/j.cell.2006.11.015.
25. Pascual-Ahuir A, Struhl K, Proft M. 2006. Genome-wide location analysis of the stress-activated MAP kinase Hog1 in yeast. Methods 40:272-278. http://dx.doi.org/10.1016/j.ymeth.2006.06.007.
26. Pokholok DK, Zeitlinger J, Hannett NM, Reynolds DB, Young RA. 2006. Activated signal transduction kinases frequently occupy target genes. Science 313:533-536. http://dx.doi.org/10.1126/science.1127677.
27. Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, Posas F. 2006. The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol. Cell 23:241-250. http://dx.doi.org/10.1016/j.molcel.2006.05.031.
28. Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB. 2003. Histone H3 phosphorylation by IKK-alpha is critical for cytokineinduced gene expression. Nature 423:655-659. http://dx.doi.org/10.1038/nature01576.
29. Sutcliffe EL, Bunting KL, He YQ, Li J, Phetsouphanh C, Seddiki N, Zafar A, Hindmarsh EJ, Parish CR, Kelleher AD, McInnes RL, Taya T, Milburn PJ, Rao S. 2011. Chromatin-associated protein kinase C-θ regulates an inducible gene expression program and microRNAs in human T lymphocytes. Mol. Cell 41:704-719. http://dx.doi.org/10.1016/j.molcel.2011.02.030.
30. Chand S, Mehta N, Bahia MS, Dixit A, Silakari O. 2012. Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders. Curr. Pharm. Des. 18: 4725-4746. http://dx.doi.org/10.2174/138161212802651625.
31. Isakov N, Altman A. 2012. PKC-theta-mediated signal delivery from the TCR/CD28 surface receptors. Front. Immunol. 3:273. http://dx.doi.org/10.3389/fimmu.2012.00273.
32. Zanin-Zhorov A, Ding Y, Kumari S, Attur M, Hippen KL, Brown M, Blazar BR, Abramson SB, Lafaille JJ, Dustin ML. 2010. Protein kinase C-theta mediates negative feedback on regulatory T cell function. Science 328:372-376. http://dx.doi.org/10.1126/science.1186068.
33. Aguilo JI, Garaude J, Pardo J, Villalba M, Anel A. 2009. Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression. J. Immunol. 182:1972-1981. http://dx.doi.org/10.4049/jimmunol.0801820.
34. Belguise K, Milord S, Galtier F, Moquet-Torcy G, Piechaczyk M, Chalbos D. 2012. The PKCtheta pathway participates in the aberrant accumulation of Fra-1 protein in invasive ER-negative breast cancer cells. Oncogene 31:4889-4897. http://dx.doi.org/10.1038/onc.2011.659.
35. Belguise K, Sonenshein GE. 2007. PKCtheta promotes c-Rel-driven mammary tumorigenesis in mice and humans by repressing estrogen receptor alpha synthesis. J. Clin. Invest. 117:4009-4021.
36. Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. 2008. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704-715. http://dx.doi.org/10.1016/j.cell.2008.03.027.
37. Sleeman JP, Thiery JP. 2011. SnapShot: the epithelial-mesenchymal transition. Cell 145:162.e1. http://dx.doi.org/10.1016/j.cell.2011.03.029.
38. Sutcliffe EL, Li J, Zafar A, Hardy K, Ghildyal R, McCuaig R, Norris NC, Lim PS, Milburn PJ, Casarotto MG, Denyer G, Rao S. 2012. Chromatinized protein kinase C-theta: can it escape the clutches of NF-kappaB? Front. Immunol. 3:260. http://dx.doi.org/10.3389/fimmu.2012.00260.
39. Chen L, Dahlstrom JE, Chandra A, Board P, Rangasamy D. 2012. Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer. Breast Cancer Res. Treat. 136:129-142. http://dx.doi.org/10.1007/s10549-012-2246-7.
40. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. 2005. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A. 102:15545-15550. http://dx.doi.org/10.1073/pnas.0506580102.
41. Simon JM, Giresi PG, Davis IJ, Lieb JD. 2012. Using formaldehydeassisted isolation of regulatory elements (FAIRE) to isolate active regulatory DNA. Nat. Protoc. 7:256-267. http://dx.doi.org/10.1038/nprot.2011.444.
42. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, KlingenhoffA, Frisch M, Bayerlein M, Werner T. 2005. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21:2933-2942. http://dx.doi.org/10.1093/bioinformatics/bti473.
43. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9:357-359. http://dx.doi.org/10.1038/nmeth.1923.
44. Rashid NU, Giresi PG, Ibrahim JG, Sun W, Lieb JD. 2011. ZINBA integrates local covariates with DNA-seq data to identify broad and narrow regions of enrichment, even within amplified genomic regions. Genome Biol. 12:R67. http://dx.doi.org/10.1186/gb-2011-12-7-r67.
45. Cairns J, Spyrou C, Stark R, Smith ML, Lynch AG, Tavare S. 2011. BayesPeak-an R package for analysing ChIP-seq data. Bioinformatics 27:713-714. http://dx.doi.org/10.1093/bioinformatics/btq685.
46. Zhu LJ, Gazin C, Lawson ND, Pages H, Lin SM, Lapointe DS, Green MR. 2010. ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data. BMC Bioinformatics 11:237. http://dx.doi.org/10.1186/1471-2105-11-237.
47. Huang W-L. 2012. Ranking gene ontology terms for predicting nonclassical secretory proteins in eukaryotes and prokaryotes. J. Theor. Biol. 312:105-113. http://dx.doi.org/10.1016/j.jtbi.2012.07.027.
48. Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW, Jeong HG. 2010. Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. Biochem. Pharmacol. 79:1714-1726. http://dx.doi.org/10.1016/j.bcp.2010.02.003.
49. Moolten FL, Schreiber B, Rizzone A, Weiss AJ, Boger E. 1981. Protection of mice against 7,12-dimethylbenz (a) anthracene-induced skin tumors by immunization with a fluorinated analog of the carcinogen. Cancer Res. 41:425-429.
50. He H, Davidson AJ, Wu D, Marshall FF, Chung LW, Zhau HE, He D, Wang R. 2010. Phorbol ester phorbol-12-myristate-13-acetate induces epithelial to mesenchymal transition in human prostate cancer ARCaPE cells. Prostate 70:1119-1126. http://dx.doi.org/10.1002/pros.21146.
51. Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, IsakoffSJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S. 2013. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339:580-584. http://dx.doi.org/10.1126/science.1228522.
52. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. 2010. Core epithelialto- mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc. Natl. Acad. Sci. U. S. A. 107:15449-15454. http://dx.doi.org/10.1073/pnas.1004900107.
53. Plasari G, Calabrese A, Dusserre Y, Gronostajski RM, McNair A, Michalik L, Mermod N. 2009. Nuclear factor I-C links platelet-derived growth factor and transforming growth factor beta1 signaling to skin wound healing progression. Mol. Cell. Biol. 29:6006-6017. http://dx.doi.org/10.1128/MCB.01921-08.
54. Verrecchia F, Chu ML, Mauviel A. 2001. Identification of novel TGFbeta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J. Biol. Chem. 276: 17058-17062. http://dx.doi.org/10.1074/jbc. M100754200.
55. Jechlinger M, Grunert S, Tamir IH, Janda E, Ludemann S, Waerner T, Seither P, Weith A, Beug H, Kraut N. 2003. Expression profiling of epithelial plasticity in tumor progression. Oncogene 22:7155-7169. http://dx.doi.org/10.1038/sj.onc.1206887.
56. Lim E, Wu D, Pal B, Bouras T, Asselin-Labat M-L, Vaillant F, Yagita H, Lindeman GJ, Smyth GK, Visvader JE. 2010. Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways. Breast Cancer Res. 12:R21. http://dx.doi.org/10.1186/bcr2560.
57. Browne EP, Wing B, Coleman D, Shenk T. 2001. Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J. Virol. 75:12319-12330. http://dx.doi.org/10.1128/JVI.75.24.12319-12330.2001.
58. Hecker M, Hartmann C, Kandulski O, Paap BK, Koczan D, Thiesen H-J, Zettl UK. 2013. Interferon-beta therapy in multiple sclerosis: the short-term and long-term effects on the patients' individual gene expression in peripheral blood. Mol. Neurobiol. 48:737-756. http://dx.doi.org/10.1007/s12035-013-8463-1.
59. Sana TR, Janatpour MJ, Sathe M, McEvoy LM, McClanahan TK. 2005. Microarray analysis of primary endothelial cells challenged with different inflammatory and immune cytokines. Cytokine 29:256-269. http://dx.doi.org/10.1016/j.cyto.2004.11.003.
60. Zhang Y, Gavriil M, Lucas J, Mandiyan S, Follettie M, Diesl V, Sum F-W, Powell D, Haney S, Abraham R, Arndt K. 2008. IkappaBalpha kinase inhibitor IKI-1 conferred tumor necrosis factor alpha sensitivity to pancreatic cancer cells and a xenograft tumor model. Cancer Res. 68: 9519-9524. http://dx.doi.org/10.1158/0008-5472.CAN-08-1549.
61. Amit I, Citri A, Shay T, Lu Y, Katz M, Zhang F, Tarcic G, Siwak D, Lahad J, Jacob-Hirsch J, Amariglio N, Vaisman N, Segal E, Rechavi G, Alon U, Mills GB, Domany E, Yarden Y. 2007. A module of negative feedback regulators defines growth factor signaling. Nat. Genet. 39:503-512. http://dx.doi.org/10.1038/ng1987.
62. Cheng J-C, Auersperg N, Leung PCK. 2012. EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a possible step in the transition to low-grade serous carcinoma cells? PLoS One 7:e34071. http://dx.doi.org/10.1371/journal.pone.0034071.
63. Ho M-Y, Tang S-J, Chuang M-J, Cha T-L, Li J-Y, Sun G-H, Sun K-H. 2012. TNF-alpha induces epithelial-mesenchymal transition of renal cell carcinoma cells via a GSK3beta-dependent mechanism. Mol. Cancer Res. 10:1109-1119. http://dx.doi.org/10.1158/1541-7786.MCR-12-0160.
64. Li C-W, Xia W, Huo L, Lim S-O, Wu Y, Hsu JL, Chao C-H, Yamaguchi H, Yang N-K, Ding Q, Wang Y, Lai Y-J, LaBaffAM, Wu T-J, Lin B-R, YangM-H, Hortobagyi GN, Hung M-C. 2012. Epithelial-mesenchymal transition induced by TNF-alpha requires NF-kappaB-mediated tran- scriptional upregulation of Twist1. Cancer Res. 72:1290-1300. http://dx.doi.org/10.1158/1538-7445.AM2012-1290.
65. Zhang S, Wang X, Iqbal S, Wang Y, Osunkoya AO, Chen Z, Chen Z, Shin DM, Yuan H, Wang YA, Zhau HE, Chung LWK, Ritenour C, Kucuk O, Wu D. 2013. Epidermal growth factor promotes protein degradation of epithelial protein lost in neoplasm (EPLIN), a putative metastasis suppressor, during epithelial-mesenchymal transition. J. Biol. Chem. 288:1469-1479. http://dx.doi.org/10.1074/jbc. M112.438341.
66. Giambra V, Jenkins CR, Wang H, Lam SH, Shevchuk OO, Nemirovsky O, Wai C, Gusscott S, Chiang MY, Aster JC, Humphries RK, Eaves C, Weng AP. 2012. NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-theta and reactive oxygen species. Nat. Med. 18:1693-1698. http://dx.doi.org/10.1038/nm.2960.
67. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Jr, Badve S, Nakshatri H. 2006. CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 8:R59. http://dx.doi.org/10.1186/bcr1610.
68. Martiny-Baron G, Kazanietz MG, Mischak H, Blumberg PM, Kochs G, Hug H, Marme D, Schachtele C. 1993. Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J. Biol. Chem. 268: 9194-9197.
69. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F. 1991. The bisindolylmaleimide GF109203X is a potent and selective inhibitor of protein kinase C. J. Biol. Chem. 266:15771-15781.
70. Coudronniere N, Villalba M, Englund N, Altman A. 2000. NF-kappa B activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-theta. Proc. Natl. Acad. Sci. U. S. A. 97:3394-3399. http://dx.doi.org/10.1073/pnas.97.7.3394.
71. Hayden MS, Ghosh S. 2008. Shared principles in NF-kappaB signaling. Cell 132:344-362. http://dx.doi.org/10.1016/j.cell.2008.01.020.
72. Lin X, O'Mahony A, Mu Y, Geleziunas R, Greene WC. 2000. Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta. Mol. Cell. Biol. 20:2933-2940. http://dx.doi.org/10.1128/MCB.20.8.2933-2940.2000.
73. Sun L, Mathews LA, Cabarcas SM, Zhang X, Yang A, Zhang Y, Young MR, Klarmann KD, Keller JR, Farrar WL. 2013. Epigenetic regulation of SOX9 by the NF-kappaB signaling pathway in pancreatic cancer stem cells. Stem Cells 31:1454-1466. http://dx.doi.org/10.1002/stem.1394.
74. Yamamoto M, Taguchi Y, Ito-Kureha T, Semba K, Yamaguchi N, Inoue J-I. 2013. NF-kappaB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype. Nat. Commun. 4:2299. http://dx.doi.org/10.1038/ncomms3299.
75. Jimenez J-M, Boyall D, Brenchley G, Collier PN, Davis CJ, Fraysse D, Keily SB, Henderson J, Miller A, Pierard F, Settimo L, Twin HC, Bolton CM, Curnock AP, Chiu P, Tanner AJ, Young S. 2013. Design and optimization of selective protein kinase C theta (PKCtheta) inhibitors for the treatment of autoimmune diseases. J. Med. Chem. 56:1799-1810. http://dx.doi.org/10.1021/jm301465a.
76. Geng H, Wittwer T, Dittrich-Breiholz O, Kracht M, Schmitz ML. 2009. Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep. 10:381-386. http://dx.doi.org/10.1038/embor.2009.10.
77. Mao X, Gluck N, Li D, Maine GN, Li H, Zaidi IW, Repaka A, Mayo MW, Burstein E. 2009. GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA. Genes Dev. 23:849-861. http://dx.doi.org/10.1101/gad.1748409.
78. Mattioli I, Geng H, Sebald A, Hodel M, Bucher C, Kracht M, Schmitz ML. 2006. Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation is mediated by IKK epsilon. J. Biol. Chem. 281:6175-6183. http://dx.doi.org/10.1074/jbc. M508045200.
79. Neumann M, Naumann M. 2007. Beyond IkappaBs: alternative regulation of NF-kappaB activity. FASEB J. 21:2642-2654. http://dx.doi.org/10.1096/fj.06-7615rev.
80. Schmitz ML, Mattioli I, Buss H, Kracht M. 2004. NF-kappaB: a multifaceted transcription factor regulated at several levels. Chembiochem 5:1348-1358. http://dx.doi.org/10.1002/cbic.200400144.
81. Iliopoulos D, Hirsch HA, Struhl K. 2009. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:693-706. http://dx.doi.org/10.1016/j.cell.2009.10.014.
82. Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA. 2013. Protein kinase C alpha is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell 24:347-364. http://dx.doi.org/10.1016/j.ccr.2013.08.005.
83. Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV. 2003. Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes. Mol. Cell. Biol. 23:7068-7081. http://dx.doi.org/10.1128/MCB.23.19.7068-7081.2003.
84. Moreno R, Sobotzik J-M, Schultz C, Schmitz ML. 2010. Specification of the NF-kappaB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKK epsilon. Nucleic Acids Res. 38:6029-6044. http://dx.doi.org/10.1093/nar/gkq439.
85. Adli M, Baldwin AS. 2006. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. J. Biol. Chem. 281:26976-26984. http://dx.doi.org/10.1074/jbc. M603133200.
86. Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Richardson AL, Greulich H, Stewart CJ, Mulvey LA, Shen RR, Ambrogio L, Hirozane-Kishikawa T, Hill DE, Vidal M, Meyerson M, Grenier JK, Hinkle G, Root DE, Roberts TM, Lander ES, Polyak K, Hahn WC. 2007. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 129:1065-1079. http://dx.doi.org/10.1016/j.cell.2007.03.052.
87. Cho KB, Cho MK, Lee WY, Kang KW. 2010. Overexpression of c-myc induces epithelial mesenchymal transition in mammary epithelial cells. Cancer Lett. 293:230-239. http://dx.doi.org/10.1016/j.canlet.2010.01.013.
88. Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schubeler D, van Nimwegen E, Christofori G. 2013. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell 23: 768-783. http://dx.doi.org/10.1016/j.ccr.2013.04.020.
89. Crook T, Nicholls JM, Brooks L, O'Nions J, Allday MJ. 2000. High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)? Oncogene 19:3439-3444. http://dx.doi.org/10.1038/sj.onc.1203656.
90. Lindsay J, McDade SS, Pickard A, McCloskey KD, McCance DJ. 2011. Role of DeltaNp63gamma in epithelial to mesenchymal transition. J. Biol. Chem. 286:3915-3924. http://dx.doi.org/10.1074/jbc. M110.162511.
91. Gervasi M, Bianchi-Smiraglia A, Cummings M, Zheng Q, Wang D, Liu S, Bakin AV. 2012. JunB contributes to Id2 repression and the epithelialmesenchymal transition in response to transforming growth factor-beta. J. Cell Biol. 196:589-603. http://dx.doi.org/10.1083/jcb.201109045.
92. Perou CM, Jeffrey SS, van de Rijn M, Rees CA, Eisen MB, Ross DT, Pergamenschikov A, Williams CF, Zhu SX, Lee JC, Lashkari D, Shalon D, Brown PO, Botstein D. 1999. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc. Natl. Acad. Sci. U. S. A. 96:9212-9217. http://dx.doi.org/10.1073/pnas.96.16.9212.
93. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale A-L, Botstein D. 2003. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl. Acad. Sci. U. S. A. 100:8418-8423. http://dx.doi.org/10.1073/pnas.0932692100.
94. Zaret KS, Carroll JS. 2011. Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 25:2227-2241. http://dx.doi.org/10.1101/gad.176826.111.
95. Kontgen F, Grumont RJ, Strasser A, Metcalf D, Li R, Tarlinton D, Gerondakis S. 1995. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes Dev. 9:1965-1977. http://dx.doi.org/10.1101/gad.9.16.1965.
96. Suhasini M, Pilz RB. 1999. Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB). Oncogene 18:7360-7369. http://dx.doi.org/10.1038/sj.onc.1203158.
97. Williams SA, Chen L-F, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC. 2006. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25:139-149. http://dx.doi.org/10.1038/sj.emboj.7600900.