CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling

Oncogene

Volumn 34, Issue 2, 2015, Pages 177-187

  Kuhnemuth B ^a   Muhlberg L ^a   Schipper, M ^b   Griesmann, H ^a   Neesse, A ^a   Milosevic, N ^a   Wissniowski, T ^a   Buchholz, M ^a   Gress, T M ^a   Michl, P ^a  

^a UNIVERSITY HOSPITAL MARBURG   (Germany)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

CUX1; macrophage polarization; NF kB; pancreatic cancer

Indexed keywords

CUX1 PROTEIN, HUMAN; HOMEODOMAIN PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NUCLEAR PROTEIN; REPRESSOR PROTEIN; TRANSCRIPTION FACTOR RELA; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL; ANTAGONISTS AND INHIBITORS; COCULTURE; DISEASE COURSE; GENETIC TRANSFECTION; GENETICS; HUMAN; MACROPHAGE; METABOLISM; MOUSE; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CARCINOMA, PANCREATIC DUCTAL; COCULTURE TECHNIQUES; DISEASE PROGRESSION; HOMEODOMAIN PROTEINS; HUMANS; MACROPHAGES; MICE; NF-KAPPA B; NUCLEAR PROTEINS; PANCREATIC NEOPLASMS; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR RELA; TRANSFECTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 84928475148     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2013.530     Document Type: Article

References (60)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin 2012; 62: 10-29.
2. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007; 6: 1186-1197.
3. Kleeff J, Beckhove P, Esposito I, Herzig S, Huber PE, Lohr JM et al. Pancreatic cancer microenvironment. Int J Cancer 2007; 121: 699-705.
4. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331: 1612-1616.
5. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 2012; 21: 822-835.
6. Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 2012; 487: 500-504.
7. Neesse A, Frese KK, Bapiro TE, Nakagawa T, Sternlicht MD, Seeley TW et al. CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer. Proc Natl Acad Sci USA 2013; 110: 12325-12330.
8. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 2007; 67: 9518-9527.
9. Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett 2009; 279: 1-7.
10. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010; 11: 889-896.
11. Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res 2011; 167: e211-e219.
12. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004; 431: 461-466.
13. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005; 5: 749-759.
14. Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 2006; 107: 2112-2122.
15. Saccani A, Schioppa T, Porta C, Biswas SK, Nebuloni M, Vago L et al. p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res 2006; 66: 11432-11440.
16. Harada R, Dufort D, Denis-Larose C, Nepveu A. Conserved cut repeats in the human cut homeodomain protein function as DNA binding domains. J Biol Chem 1994; 269: 2062-2067.
17. Sansregret L, Nepveu A. The multiple roles of CUX1: insights from mouse models and cell-based assays. Gene 2008; 412: 84-94.
18. Michl P, Ramjaun AR, Pardo OE, Warne PH, Wagner M, Poulsom R et al. CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness. Cancer Cell 2005; 7: 521-532.
19. Ripka S, Neesse A, Riedel J, Bug E, Aigner A, Poulsom R et al. CUX1: target of Akt signalling and mediator of resistance to apoptosis in pancreatic cancer. Gut 2010; 59: 1101-1110.
20. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005; 7: 469-483.
21. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI et al. Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 1993; 105: 1846-1856.
22. Fragiadaki M, Ikeda T, Witherden A, Mason RM, Abraham D, Bou-Gharios G. High doses of TGF-beta potently suppress type I collagen via the transcription factor CUX1. Mol Biol Cell 2011; 22: 1836-1844.
23. De Vos J, Thykjaer T, Tarte K, Ensslen M, Raynaud P, Requirand G et al. Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays. Oncogene 2002; 21: 6848-6857.
24. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006; 66: 605-612.
25. Ueda Y, Su Y, Richmond A. CCAAT displacement protein regulates nuclear factorkappa beta-mediated chemokine transcription in melanoma cells. Melanoma Res 2007; 17: 91-103.
26. Nepveu A. Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development. Gene 2001; 270: 1-15.
27. Huang LY, Dumontelle JL, Zolodz M, Deora A, Mozier NM, Golding B. Use of tolllike receptor assays to detect and identify microbial contaminants in biological products. J Clin Microbiol 2009; 47: 3427-3434.
28. Schmitz ML, Mattioli I, Buss H, Kracht M. NF-kappaB: a multifaceted transcription factor regulated at several levels. Chembiochem: E J Chem Biol 2004; 5: 1348-1358.
29. Li S, Moy L, Pittman N, Shue G, Aufiero B, Neufeld EJ et al. Transcriptional repression of the cystic fibrosis transmembrane conductance regulator gene, mediated by CCAAT displacement protein/cut homolog, is associated with histone deacetylation. J Biol Chem 1999; 274: 7803-7815.
30. Li S, Aufiero B, Schiltz RL, Walsh MJ. Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREBbinding protein (CBP)-associated factor and CBP. Proc Natl Acad Sci USA 2000; 97: 7166-7171.
31. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677-686.
32. Catt D, Hawkins S, Roman A, Luo W, Skalnik DG. Overexpression of CCAAT displacement protein represses the promiscuously active proximal gp91(phox) promoter. Blood 1999; 94: 3151-3160.
33. Nirodi C, Hart J, Dhawan P, Moon NS, Nepveu A, Richmond A. The role of CDP in the negative regulation of CXCL1 gene expression. J Biol Chem 2001; 276: 26122-26131.
34. Mihaly Z, Kormos M, Lanczky A, Dank M, Budczies J, Szasz MA et al. A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer. Breast cancer Res Treat 2013; 140: 219-232.
35. Liu M, Guo S, Stiles JK. The emerging role of CXCL10 in cancer (Review). Oncology Lett 2011; 2: 583-589.
36. Chen LF, Greene WC. Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation. J Mol Med 2003; 81: 549-557.
37. Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science 2001; 293: 1653-1657.
38. Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 2002; 21: 6539-6548.
39. Sheppard KA, Rose DW, Haque ZK, Kurokawa R, McInerney E, Westin S et al. Transcriptional activation by NF-kappaB requires multiple coactivators. Mol Cell Biol 1999; 19: 6367-6378.
40. Ashburner BP, Westerheide SD, Baldwin Jr. AS. The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol Cell Biol 2001; 21: 7065-7077.
41. Zhang W, Kone BC. NF-kappaB inhibits transcription of the H(\+)-K(\+)-ATPase alpha(2)-subunit gene: role of histone deacetylases. Am J Physiol Renal Physiol 2002; 283: F904-F911.
42. Sharma M, Brantley JG, Vassmer D, Chaturvedi G, Baas J, Vanden Heuvel GB. The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development. Gene 2009; 439: 87-94.
43. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004; 118: 285-296.
44. Maeda S, Kamata H, Luo JL, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005; 121: 977-990.
45. Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J et al. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol 2000; 164: 762-767.
46. Biswas SK, Sica A, Lewis CE. Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J Immunol 2008; 180: 2011-2017.
47. Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 2007; 117: 1155-1166.
48. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958-969.
49. Tsunawaki S, Sporn M, Ding A, Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature 1988; 334: 260-262.
50. Yoshikawa K, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Gotohda N et al. Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head. Cancer Sci 2012; 103: 2012-2020.
51. Benson DD, Meng X, Fullerton DA, Moore EE, Lee JH, Ao L et al. Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma. Am J Physiol Regul, Integr Comp Physiol 2012; 302: R1067-R1075.
52. Menen RS, Hassanein MK, Momiyama M, Suetsugu A, Moossa AR, Hoffman RM et al. Tumor-educated macrophages promote tumor growth and peritoneal metastasis in an orthotopic nude mouse model of human pancreatic cancer. In vivo 2012; 26: 565-569.
53. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factorbeta regulation of immune responses. Annu Rev Immunol 2006; 24: 99-146.
54. Bogdan C, Paik J, Vodovotz Y, Nathan C. Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem 1992; 267: 23301-23308.
55. Werner F, Jain MK, Feinberg MW, Sibinga NE, Pellacani A, Wiesel P et al. Transforming growth factor-beta 1 inhibition of macrophage activation is mediated via Smad3. J Biol Chem 2000; 275: 36653-36658.
56. Darsigny M, St-Jean S, Boudreau F. Cux1 transcription factor is induced in inflammatory bowel disease and protects against experimental colitis. Inflamm Bowel Dis 2010; 16: 1739-1750.
57. Cadieux C, Kedinger V, Yao L, Vadnais C, Drossos M, Paquet M et al. Mouse mammary tumor virus p75 and p110 CUX1 transgenic mice develop mammary tumors of various histologic types. Cancer Res 2009; 69: 7188-7197.
58. Kedinger V, Sansregret L, Harada R, Vadnais C, Cadieux C, Fathers K et al. p110 CUX1 homeodomain protein stimulates cell migration and invasion in part through a regulatory cascade culminating in the repression of E-cadherin and occludin. J Biol Chem 2009; 284: 27701-27711.
59. Baumgart S, Glesel E, Singh G, Chen NM, Reutlinger K, Zhang J et al. Restricted heterochromatin formation links NFATc2 repressor activity with growth promotion in pancreatic cancer. Gastroenterology 2012; 142: e381-e387.
60. Huth J, Buchholz M, Kraus JM, Schmucker M, von Wichert G, Krndija D et al. Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system. BMC Cell Biol 2010; 11: 24.