Epithelial hypoxia-inducible factor 2α facilitates the progression of colon tumors through recruiting neutrophils

Molecular and Cellular Biology

Volumn 37, Issue 5, 2017, Pages

  Triner, Daniel ^c   Xue, Xiang ^c   Schwartz, Andrew J ^c   Jung, Inkyung ^c   Colacino, Justin A ^a,b   Shah, Yatrik M ^c,d  

^a Nutritional Sciences   (United States)

^b Departments of Molecular and Integrative Physiology   (United States)

^c Division of Gastroenterology   (United States)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Cancer; Colon; Colon cancer; HIF 2 ; Hypoxia; Inflammation; Neutrophils

Indexed keywords

CXCL1 CHEMOKINE; HYPOXIA INDUCIBLE FACTOR 2ALPHA; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; C-MYC-ASSOCIATED ZINC FINGER PROTEIN; DNA BINDING PROTEIN; ENDOTHELIAL PAS DOMAIN-CONTAINING PROTEIN 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; TRANSCRIPTION FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COLON CARCINOGENESIS; COLON TUMOR; CONTROLLED STUDY; EPITHELIUM CELL; INTESTINE EPITHELIUM; MOUSE; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA SEQUENCE; SEQUENCE ANALYSIS; TUMOR GROWTH; TUMOR MICROENVIRONMENT; ANIMAL; CARCINOGENESIS; CHEMOTAXIS; COLITIS; COMPLICATION; DISEASE COURSE; GENE EXPRESSION REGULATION; GENETICS; INFLAMMATION; INTESTINE MUCOSA; METABOLISM; NEUTROPHIL; PATHOLOGY; PROMOTER REGION;

ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARCINOGENESIS; CHEMOKINE CXCL1; CHEMOTAXIS; COLITIS; COLONIC NEOPLASMS; DISEASE PROGRESSION; DNA-BINDING PROTEINS; EPITHELIAL CELLS; GENE EXPRESSION REGULATION, NEOPLASTIC; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INFLAMMATION; INTESTINAL MUCOSA; MICE; NEUTROPHIL INFILTRATION; NEUTROPHILS; PROMOTER REGIONS, GENETIC; TRANSCRIPTION FACTORS;

EID: 85013883423     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00481-16     Document Type: Article

References (57)

1. Siegel RL, Miller KD, Jemal A. 2016. Cancer statistics, 2016. CA Cancer J Clin 66:7-30. https://doi.org/10.3322/caac.21332.
2. Kim ER, Chang DK. 2014. Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis. World J Gastroenterol 20:9872-9881. https://doi.org/10.3748/wjg.v20.i29.9872.
3. Fearon ER. 2011. Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479 -507. https://doi.org/10.1146/annurev-pathol-011110 -130235.
4. Robles AI, Traverso G, Zhang M, Roberts NJ, Khan MA, Joseph C, Lauwers GY, Selaru FM, Popoli M, Pittman ME, Ke X, Hruban RH, Meltzer SJ, Kinzler KW, Vogelstein B, Harris CC, Papadopoulos N. 2016. Whole-exome sequencing analyses of inflammatory bowel disease-associated colorectal cancers. Gastroenterology 150:931-943. https://doi.org/10.1053/ j.gastro.2015.12.036.
5. Terzić J, Grivennikov S, Karin E, Karin M. 2010. Inflammation and colon cancer. Gastroenterology 138:2101-2114. https://doi.org/10.1053/ j.gastro.2010.01.058.
6. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL. 2000. The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumorassociated macrophages. Am J Pathol 157:411- 421. https://doi.org/ 10.1016/S0002-9440(10)64554-3.
7. Semenza GL. 2012. Hypoxia-inducible factors in physiology and medicine. Cell 148:399-408. https://doi.org/10.1016/j.cell.2012.01.021.
8. Semenza GL. 2012. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 33: 207-214. https://doi.org/10.1016/j.tips.2012.01.005.
9. Xue X, Taylor M, Anderson E, Hao C, Qu A, Greenson JK, Zimmermann EM, Gonzalez FJ, Shah YM. 2012. Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis. Cancer Res 72:2285-2293. https://doi.org/10.1158/0008-5472.CAN -11-3836.
10. Xue X, Ramakrishnan S, Anderson E, Taylor M, Zimmermann EM, Spence JR, Huang S, Greenson JK, Shah YM. 2013. Endothelial PAS domain protein 1 activates the inflammatory response in the intestinal epithelium to promote colitis in mice. Gastroenterology 145:831- 841. https:// doi.org/10.1053/j.gastro.2013.07.010.
11. Fridlender ZG, Albelda SM. 2012. Tumor-associated neutrophils: friend or foe? Carcinogenesis 33:949 -955. https://doi.org/10.1093/carcin/bgs123.
12. Rao H-L, Chen J-W, Li M, Xiao Y-B, Fu J, Zeng Y-X, Cai M-Y, Xie D. 2012. Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis. PLoS One 7:e30806. https://doi.org/10.1371/journal.pone .0030806.
13. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM. 2009. Polarization of tumor-associated neutrophil (TAN) phenotype by TGF-α: "N1" versus "N2" TAN. Cancer Cell 16:183-194. https://doi.org/10.1016/j.ccr.2009.06.017.
14. Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, Stolz DB, Land SR, Marconcini LA, Kliment CR, Jenkins KM, Beaulieu KA, Mouded M, Frank SJ, Wong KK, Shapiro SD. 2010. Neutrophil elastasemediated degradation of IRS-1 accelerates lung tumor growth. Nat Med 16:219 -223. https://doi.org/10.1038/nm.2084.
15. Nozawa H, Chiu C, Hanahan D. 2006. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A 103:12493-12498. https://doi.org/10.1073/ pnas.0601807103.
16. Mishalian I, Bayuh R, Eruslanov E, Michaeli J, Levy L, Zolotarov L, Singhal S, Albelda SM, Granot Z, Fridlender ZG. 2014. Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17-a new mechanism of impaired antitumor immunity. Int J Cancer 135:1178 -1186. https:// doi.org/10.1002/ijc.28770.
17. Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. 2014. Tumorassociated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest 124:5466 -5480. https://doi.org/10.1172/ JCI77053.
18. Taketo MM, Edelmann W. 2009. Mouse models of colon cancer. Gastroenterology 136:780 -798. https://doi.org/10.1053/j.gastro.2008.12.049.
19. Tanaka T, Kohno H, Suzuki R, Hata K, Sugie S, Niho N, Sakano K, Takahashi M, Wakabayashi K. 2006. Dextran sodium sulfate strongly promotes colorectal carcinogenesis in ApcMin/α mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms. Int J Cancer 118:25-34. https://doi.org/10.1002/ ijc.21282.
20. Pruenster M, Kurz ARM, Chung K-J, Cao-Ehlker X, Bieber S, Nussbaum CF, Bierschenk S, Eggersmann TK, Rohwedder I, Heinig K, Immler R, Moser M, Koedel U, Gran S, McEver RP, Vestweber D, Verschoor A, Leanderson T, Chavakis T, Roth J, Vogl T, Sperandio M. 2015. Extracellular MRP8/14 is a regulator of α2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun 6:6915. https://doi.org/10.1038/ncomms7915.
21. Taylor M, Qu A, Anderson ER, Matsubara T, Martin A, Gonzalez FJ, Shah YM. 2011. Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology 140:2044 -2055. https://doi.org/10.1053/j.gastro.2011.03.007.
22. Shah YM, Ito S, Morimura K, Chen C, Yim S-H, Haase VH, Gonzalez FJ. 2008. Hypoxia-inducible factor augments experimental colitis through a MIF-dependent inflammatory signaling cascade. Gastroenterology 134: 2036-2048. https://doi.org/10.1053/j.gastro.2008.03.009.
23. Powell DR, Huttenlocher A. 2016. Neutrophils in the tumor microenvironment. Trends Immunol 37:41-52. https://doi.org/10.1016/j.it.2015 .11.008.
24. Isella C, Terrasi A, Bellomo SE, Petti C, Galatola G, Muratore A, Mellano A, Senetta R, Cassenti A, Sonetto C, Inghirami G, Trusolino L, Fekete Z, De Ridder M, Cassoni P, Storme G, Bertotti A, Medico E. 2015. Stromal contribution to the colorectal cancer transcriptome. Nat Genet 47: 312-319. https://doi.org/10.1038/ng.3224.
25. Dame MK, Jiang Y, Appelman HD, Copley KD, McClintock SD, Aslam MN, Attili D, Elmunzer BJ, Brenner DE, Varani J, Turgeon DK. 2014. Human colonic crypts in culture: segregation of immunochemical markers in normal versus adenoma-derived. Lab Invest 94:222-234. https://doi.org/ 10.1038/labinvest.2013.145.
26. Ramakrishnan SK, Anderson ER, Martin A, Centofanti B, Shah YM. 2015. Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice. Proc Natl Acad Sci U S A 112:E3738 -E3747. https:// doi.org/10.1073/pnas.1504891112.
27. Hu C-J, Sataur A, Wang L, Chen H, Simon MC. 2007. The N-terminal transactivation domain confers target gene specificity of hypoxiainducible factors HIF-1α and HIF-2α. Mol Biol Cell 18:4528-4542. https:// doi.org/10.1091/mbc.E06-05-0419.
28. Finisguerra V, Di Conza G, Di Matteo M, Serneels J, Costa S, Thompson AAR, Wauters E, Walmsley S, Prenen H, Granot Z, Casazza A, Mazzone M. MET is required for the recruitment of anti-tumoural neutrophils. Nature 522:349 -353. https://doi.org/10.1038/nature14407.
29. Xie L, Xue X, Taylor M, Ramakrishnan SK, Nagaoka K, Hao C, Gonzalez FJ, Shah YM. 2014. Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon permeability through suppression of occludin, leading to hypoxia-induced inflammation. Mol Cell Biol 34: 3013-3023. https://doi.org/10.1128/MCB.00324-14.
30. Smits M, Wurdinger T, van het Hof B, Drexhage JAR, Geerts D, Wesseling P, Noske DP, Vandertop WP, de Vries HE, Reijerkerk A. 2012. Mycassociated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB J 26: 2639-2647. https://doi.org/10.1096/fj.11-202820.
31. Kaneider NC, Agarwal A, Leger AJ, Kuliopulos A. 2005. Reversing systemic inflammatory response syndrome with chemokine receptor pepducins. Nat Med 11:661- 665. https://doi.org/10.1038/nm1245.
32. Steele CW, Karim SA, Foth M, Rishi L, Leach JDG, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJB, Sansom OJ, Morton JP. 2015. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation. J Pathol 237:85-97. https://doi.org/10.1002/path.4555.
33. Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau C-S, Verstegen NJM, Ciampricotti M, Hawinkels LJAC, Jonkers J, de Visser KE. IL17-producing T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522:345-348. https://doi.org/10.1038/ nature14282.
34. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang L-P, Gimotty PA, Gilks CB, Lal P, Zhang L, Coukos G. 2011. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells. Nature 475:226 -230. https://doi.org/10.1038/nature10169.
35. Lee KE, Spata M, Bayne LJ, Buza EL, Durham AC, Allman D, Vonderheide RH, Simon MC. 2016. Hif1α deletion reveals pro-neoplastic function of B cells in pancreatic neoplasia. Cancer Discov 6:256 -269. https://doi.org/ 10.1158/2159-8290.CD-15-0822.
36. Zhou S-L, Zhou Z-J, Hu Z-Q, Huang X-W, Wang Z, Chen E-B, Fan J, Cao Y, Dai Z, Zhou J. 2016. Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology 150: 1646-1658. https://doi.org/10.1053/j.gastro.2016.02.040.
37. Blaisdell A, Crequer A, Columbus D, Daikoku T, Mittal K, Dey Sudhansu K, Erlebacher A. 2015. Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells. Cancer Cell 28:785-799. https://doi.org/10.1016/j.ccell.2015.11.005.
38. Zlotnik A, Yoshie O. 2000. Chemokines: a new classification system and their role in immunity. Immunity 12:121-127. https://doi.org/10.1016/ S1074-7613(00)80165-X.
39. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD, Diehn M, West RB, Plevritis SK, Alizadeh AA. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 21:938 -945. https://doi.org/10.1038/ nm.3909.
40. Shang K, Bai Y-P, Wang C, Wang Z, Gu H-Y, Du X, Zhou X-Y, Zheng C-L, Chi Y-Y, Mukaida N, Li Y-Y. 2012. Crucial involvement of tumorassociated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice. PLoS One 7:e51848. https://doi.org/10.1371/ journal.pone.0051848.
41. Pine JK, Morris E, Hutchins GG, West NP, Jayne DG, Quirke P, Prasad KR. 2015. Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour. Br J Cancer 113:204 -211. https://doi.org/10.1038/ bjc.2015.87.
42. Steele Colin W, Karim Saadia A, Leach Joshua DG, Bailey P, Upstill- Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido Juliana B, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TRJ, Strathdee D, Biankin AV, Nibbs RJB, Barry ST, Sansom OJ, Morton JP. 2016. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 29:832- 845. https://doi.org/ 10.1016/j.ccell.2016.04.014.
43. Katoh H, Wang D, Daikoku T, Sun H, Dey SK, DuBois RN. 2013. CXCR2- expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell 24:631- 644. https:// doi.org/10.1016/j.ccr.2013.10.009.
44. Campbell EL, Bruyninckx WJ, Kelly CJ, Glover LE, McNamee EN, Bowers BE, Bayless AJ, Scully M, Saeedi BJ, Golden-Mason L, Ehrentraut SF, Curtis VF, Burgess A, Garvey JF, Sorensen A, Nemenoff R, Jedlicka P, Taylor CT, Kominsky DJ, Colgan SP. 2014. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity 40:66 -77. https://doi.org/ 10.1016/j.immuni.2013.11.020.
45. Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. 2004. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest 114:1098 -1106. https://doi.org/ 10.1172/JCI200421086.
46. Furuta GT, Turner JR, Taylor CT, Hershberg RM, Comerford K, Narravula S, Podolsky DK, Colgan SP. 2001. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med 193:1027-1034. https://doi.org/10.1084/jem.193 .9.1027.
47. Xue X, Shah YM. 2013. Hypoxia-inducible factor-2α is essential in activating the COX2/mPGES-1/PGE(2) signaling axis in colon cancer. Carcinogenesis 34:163-169. https://doi.org/10.1093/carcin/bgs313.
48. Xue X, Ramakrishnan SK, Shah YM. 2014. Activation of HIF-1α does not increase intestinal tumorigenesis. Am J Physiol 307:G187-G195.
49. Raval RR, Lau KW, Tran MGB, Sowter HM, Mandriota SJ, Li J-L, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ. 2005. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindauassociated renal cell carcinoma. Mol Cell Biol 25:5675-5686. https:// doi.org/10.1128/MCB.25.13.5675-5686.2005.
50. Criscimanna A, Duan L-J, Rhodes JA, Fendrich V, Wickline E, Hartman DJ, Monga SPS, Lotze MT, Gittes GK, Fong G-H, Esni F. 2013. PanIN-specific regulation of Wnt signaling by HIF2α during early pancreatic tumorigenesis. Cancer Res 73:4781- 4790. https://doi.org/10.1158/0008 -5472.CAN-13-0566.
51. Mazumdar J, Hickey MM, Pant DK, Durham AC, Sweet-Cordero A, Vachani A, Jacks T, Chodosh LA, Kissil JL, Simon MC, Keith B. 2010. HIF-2α deletion promotes Kras-driven lung tumor development. Proc Natl Acad Sci U S A 107:14182-14187. https://doi.org/10.1073/pnas.1001296107.
52. Scheuermann TH, Li Q, Ma H-W, Key J, Zhang L, Chen R, Garcia JA, Naidoo J, Longgood J, Frantz DE, Tambar UK, Gardner KH, Bruick RK. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat Chem Biol 9:271-276. https://doi.org/10.1038/nchembio .1185.
53. Jamieson T, Clarke M, Steele CW, Samuel MS, Neumann J, Jung A, Huels D, Olson MF, Das S, Nibbs RJB, Sansom OJ. 2012. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J Clin Invest 122:3127-3144. https://doi.org/10.1172/JCI61067.
54. Langmead B, Trapnell C, Pop M, Salzberg SL. 2009. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10:R25. https://doi.org/10.1186/gb-2009-10-3-r25.
55. Trapnell C, Pachter L, Salzberg SL. 2009. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25:1105-1111. https://doi.org/ 10.1093/bioinformatics/btp120.
56. Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L. 2013. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol 31:46 -53. https://doi.org/10.1038/ nbt.2450.
57. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289 -300.