The Myc 3′ Wnt-Responsive Element Suppresses Colonic Tumorigenesis

REFERENCES

• Archbold HC, Yang YX, Chen L, Cadigan KM. 2012. How do they do Wnt they do? Regulation of transcription by the Wnt/beta-catenin pathway. Acta Physiol. (Oxf.) 204:74–109. http://dx.doi.org/10.1111/j.1748-1716.2011.02293.x.
   PubMed Web of Science ®Google Scholar
• Yeung TM, Chia LA, Kosinski CM, Kuo CJ. 2011. Regulation of self-renewal and differentiation by the intestinal stem cell niche. Cell. Mol. Life Sci. 68:2513–2523. http://dx.doi.org/10.1007/s00018-011-0687-5.
   PubMed Web of Science ®Google Scholar
• Clevers H, Nusse R. 2012. Wnt/beta-catenin signaling and disease. Cell 149:1192–1205. http://dx.doi.org/10.1016/j.cell.2012.05.012.
   PubMed Web of Science ®Google Scholar
• MacDonald BT, Tamai K, He X. 2009. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17:9–26. http://dx.doi.org/10.1016/j.devcel.2009.06.016.
   PubMed Web of Science ®Google Scholar
• Mosimann C, Hausmann G, Basler K. 2009. Beta-catenin hits chromatin: regulation of Wnt target gene activation. Nat. Rev. Mol. Cell Biol. 10:276–286. http://dx.doi.org/10.1038/nrm2654.
   PubMed Web of Science ®Google Scholar
• He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. 1998. Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512. http://dx.doi.org/10.1126/science.281.5382.1509.
   PubMed Web of Science ®Google Scholar
• Yochum GS, Cleland R, Goodman RH. 2008. A genome-wide screen for beta-catenin binding sites identifies a downstream enhancer element that controls c-Myc gene expression. Mol. Cell. Biol. 28:7368–7379. http://dx.doi.org/10.1128/MCB.00744-08.
   PubMed Web of Science ®Google Scholar
• Dang CV, O'Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. 2006. The c-Myc target gene network. Semin. Cancer Biol. 16:253–264. http://dx.doi.org/10.1016/j.semcancer.2006.07.014.
   PubMed Web of Science ®Google Scholar
• Eilers M, Eisenman RN. 2008. Myc's broad reach. Genes Dev. 22:2755–2766. http://dx.doi.org/10.1101/gad.1712408.
   PubMed Web of Science ®Google Scholar
• Fearon ER. 2011. Molecular genetics of colorectal cancer. Annu. Rev. Pathol. 6:479–507. http://dx.doi.org/10.1146/annurev-pathol-011110-130235.
   PubMed Web of Science ®Google Scholar
• Athineos D, Sansom OJ. 2010. Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine. Oncogene 29:2585–2590. http://dx.doi.org/10.1038/onc.2010.5.
   PubMed Web of Science ®Google Scholar
• Ignatenko NA, Holubec H, Besselsen DG, Blohm-Mangone KA, Padilla-Torres JL, Nagle RB, de Alboranc IM, Guillen RJ, Gerner EW. 2006. Role of c-Myc in intestinal tumorigenesis of the ApcMin/+ mouse. Cancer Biol. Ther. 5:1658–1664. http://dx.doi.org/10.4161/cbt.5.12.3376.
   PubMed Web of Science ®Google Scholar
• Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos D, Clevers H, Clarke AR. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446:676–679. http://dx.doi.org/10.1038/nature05674.
   PubMed Web of Science ®Google Scholar
• Wilkins JA, Sansom OJ. 2008. C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine. Cancer Res. 68:4963–4966. http://dx.doi.org/10.1158/0008-5472.CAN-07-5558.
   PubMed Web of Science ®Google Scholar
• Yekkala K, Baudino TA. 2007. Inhibition of intestinal polyposis with reduced angiogenesis in ApcMin/+ mice due to decreases in c-Myc expression. Mol. Cancer Res. 5:1296–1303. http://dx.doi.org/10.1158/1541-7786.MCR-07-0232.
   PubMedGoogle Scholar
• Bottomly D, Kyler SL, McWeeney SK, Yochum GS. 2010. Identification of beta-catenin binding regions in colon cancer cells using ChIP-Seq. Nucleic Acids Res. 38:5735–5745. http://dx.doi.org/10.1093/nar/gkq363.
   PubMedGoogle Scholar
• Yochum GS, McWeeney S, Rajaraman V, Cleland R, Peters S, Goodman RH. 2007. Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells. Proc. Natl. Acad. Sci. U. S. A. 104:3324–3329. http://dx.doi.org/10.1073/pnas.0611576104.
   PubMedGoogle Scholar
• Yochum GS, Sherrick CM, MacPartlin M, Goodman RH. 2010. A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5′ and 3′ Wnt responsive enhancers. Proc. Natl. Acad. Sci. U. S. A. 107:145–150. http://dx.doi.org/10.1073/pnas.0912294107.
   PubMed Web of Science ®Google Scholar
• Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao KL, Kehoe SM, Lenz HJ, Haiman CA, Yan CL, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML. 2009. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 41:882–884. http://dx.doi.org/10.1038/ng.403.
   PubMed Web of Science ®Google Scholar
• Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Bjorklund M, Wei GH, Yan J, Niittymaki I, Mecklin JP, Jarvinen H, Ristimaki A, Di-Bernardo M, East P, Carvajal-Carmona L, Houlston RS, Tomlinson I, Palin K, Ukkonen E, Karhu A, Taipale J, Aaltonen LA. 2009. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat. Genet. 41:885–890. http://dx.doi.org/10.1038/ng.406.
   PubMed Web of Science ®Google Scholar
• Wright JB, Brown SJ, Cole MD. 2010. Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol. Cell. Biol. 30:1411–1420. http://dx.doi.org/10.1128/MCB.01384-09.
   PubMedGoogle Scholar
• Haiman CA, Le Marchand L, Yamamato J, Stram DO, Sheng X, Kolonel LN, Wu AH, Reich D, Henderson BE. 2007. A common genetic risk factor for colorectal and prostate cancer. Nat. Genet. 39:954–956. http://dx.doi.org/10.1038/ng2098.
   PubMed Web of Science ®Google Scholar
• Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier B, Houlston R, Consortium C. 2007. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 39:984–988. http://dx.doi.org/10.1038/ng2085.
   PubMed Web of Science ®Google Scholar
• Zanke BW, Greenwood CMT, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P, Sundararajan S, Roumy S, Olivier JF, Robidoux F, Sladek R, Montpetit A, Campbell P, Bezieau S, O'Shea AM, Zogopoulos G, Cotterchio M, Newcomb P, McLaughlin J, Younghusband B, Green R, Green J, Porteous MEM, Campbell H, Blanche H, Sahbatou M, Tubacher E, Bonaiti-Pellie C, Buecher B, Riboli E, Kury S, Chanock SJ, Potter J, Thomas G, Gallinger S, Hudson TJ, Dunlop MG. 2007. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat. Genet. 39:989–994. http://dx.doi.org/10.1038/ng2089.
   PubMed Web of Science ®Google Scholar
• Ahmadiyeh N, Pomerantz MM, Grisanzio C, Herman P, Jia L, Almendro V, He HH, Brown M, Liu XS, Davis M, Caswell JL, Beckwith CA, Hills A, MacConaill L, Coetzee GA, Regan MM, Freedman ML. 2010. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc. Natl. Acad. Sci. U. S. A. 107:9742–9746. http://dx.doi.org/10.1073/pnas.0910668107.
   PubMed Web of Science ®Google Scholar
• Sotelo J, Esposito D, Duhagon MA, Banfield K, Mehalko J, Liao HL, Stephens RM, Harris TJR, Munroe DJ, Wu XL. 2010. Long-range enhancers on 8q24 regulate c-Myc. Proc. Natl. Acad. Sci. U. S. A. 107:3001–3005. http://dx.doi.org/10.1073/pnas.0906067107.
   PubMedGoogle Scholar
• Yochum GS. 2011. Multiple Wnt/beta-catenin responsive enhancers align with the MYC promoter through long-range chromatin loops. PLoS One 6:e18966. http://dx.doi.org/10.1371/journal.pone.0018966.
   PubMedGoogle Scholar
• Konsavage WM, Jin G, Yochum GS. 2012. The Myc 3′ Wnt-responsive element regulates homeostasis and regeneration in the mouse intestinal tract. Mol. Cell. Biol. 32:3891–3902. http://dx.doi.org/10.1128/MCB.00548-12.
   PubMedGoogle Scholar
• Sur IK, Hallikas O, Vaharautio A, Yan J, Turunen M, Enge M, Taipale M, Karhu A, Aaltonen LA, Taipale J. 2012. Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors. Science 338:1360–1363. http://dx.doi.org/10.1126/science.1228606.
   PubMed Web of Science ®Google Scholar
• Konsavage WMJr, Roper JN, Ishmael FT, Yochum GS. 2013. The Myc 3′ Wnt responsive element regulates neutrophil recruitment after acute colonic injury in mice. Dig. Dis. Sci. 58:2858–2867. http://dx.doi.org/10.1007/s10620-013-2686-x.
   PubMedGoogle Scholar
• Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H. 2011. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141:1762–1772. http://dx.doi.org/10.1053/j.gastro.2011.07.050.
   PubMed Web of Science ®Google Scholar
• Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. 2009. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–611. http://dx.doi.org/10.1038/nature07602.
   PubMed Web of Science ®Google Scholar
• Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M. 2004. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296. http://dx.doi.org/10.1016/j.cell.2004.07.013.
   PubMed Web of Science ®Google Scholar
• Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, Heck AJ, Clevers H. 2009. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 28:3329–3340. http://dx.doi.org/10.1038/emboj.2009.285.
   PubMed Web of Science ®Google Scholar
• Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF. 1992. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256:668–670. http://dx.doi.org/10.1126/science.1350108.
   PubMed Web of Science ®Google Scholar
• Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA. 2012. Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151:56–67. http://dx.doi.org/10.1016/j.cell.2012.08.026.
   PubMed Web of Science ®Google Scholar
• Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W, Wang R, Green DR, Tessarollo L, Casellas R, Zhao K, Levens D. 2012. c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell 151:68–79. http://dx.doi.org/10.1016/j.cell.2012.08.033.
   PubMed Web of Science ®Google Scholar
• Finch AJ, Soucek L, Junttila MR, Swigart LB, Evan GI. 2009. Acute overexpression of Myc in intestinal epithelium recapitulates some but not all the changes elicited by Wnt/beta-catenin pathway activation. Mol. Cell. Biol. 29:5306–5315. http://dx.doi.org/10.1128/MCB.01745-08.
   PubMedGoogle Scholar
• Murphy DJ, Junttila MR, Pouyet L, Karnezis A, Shchors K, Bui DA, Brown-Swigart L, Johnson L, Evan GI. 2008. Distinct thresholds govern Myc's biological output in vivo. Cancer Cell 14:447–457. http://dx.doi.org/10.1016/j.ccr.2008.10.018.
   PubMed Web of Science ®Google Scholar
• Sancho E, Batlle E, Clevers H. 2004. Signaling pathways in intestinal development and cancer. Annu. Rev. Cell Dev. Biol. 20:695–723. http://dx.doi.org/10.1146/annurev.cellbio.20.010403.092805.
   PubMed Web of Science ®Google Scholar
• Heintzman ND, Stuart RK, Hon G, Fu YT, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu CX, Ching KA, Wang W, Weng ZP, Green RD, Crawford GE, Ren B. 2007. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39:311–318. http://dx.doi.org/10.1038/ng1966.
   PubMed Web of Science ®Google Scholar
• Sierra J, Yoshida T, Joazeiro CA, Jones KA. 2006. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 20:586–600. http://dx.doi.org/10.1101/gad.1385806.
   PubMed Web of Science ®Google Scholar
• Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H. 1997. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787. http://dx.doi.org/10.1126/science.275.5307.1784.
   PubMed Web of Science ®Google Scholar
• Clevers H. 2013. The intestinal crypt, a prototype stem cell compartment. Cell 154:274–284. http://dx.doi.org/10.1016/j.cell.2013.07.004.
   PubMed Web of Science ®Google Scholar
• Hinoi T, Akyol A, Theisen BK, Ferguson DO, Greenson JK, Williams BO, Cho KR, Fearon ER. 2007. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res. 67:9721–9730. http://dx.doi.org/10.1158/0008-5472.CAN-07-2735.
   PubMed Web of Science ®Google Scholar
• Hryniuk A, Grainger S, Savory JG, Lohnes D. 2012. Cdx function is required for maintenance of intestinal identity in the adult. Dev. Biol. 363:426–437. http://dx.doi.org/10.1016/j.ydbio.2012.01.010.
   PubMed Web of Science ®Google Scholar
• Verzi MP, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, Freed E, Lynch JP, Dang DT, Brown M, Clevers H, Liu XS, Shivdasani RA. 2010. TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc. Natl. Acad. Sci. U. S. A. 107:15157–15162. http://dx.doi.org/10.1073/pnas.1003822107.
   PubMedGoogle Scholar
• Stewart J, Evan G, Watson J, Sikora K. 1986. Detection of the c-myc oncogene product in colonic polyps and carcinomas. Br. J. Cancer 53:1–6. http://dx.doi.org/10.1038/bjc.1986.1.
   PubMedGoogle Scholar
• Sugio K, Kurata S, Sasaki M, Soejima J, Sasazuki T. 1988. Differential expression of c-myc gene and c-fos gene in premalignant and malignant tissues from patients with familial polyposis coli. Cancer Res. 48:4855–4861.
   PubMedGoogle Scholar
• Tsuboi K, Hirayoshi K, Takeuchi K, Sabe H, Shimada Y, Ohshio G, Tobe T, Hatanaka M. 1987. Expression of the c-myc gene in human gastrointestinal malignancies. Biochem. Biophys. Res. Commun. 146:699–704. http://dx.doi.org/10.1016/0006-291X(87)90585-7.
   PubMedGoogle Scholar
• Takahashi M, Nakatsugi S, Sugimura T, Wakabayashi K. 2000. Frequent mutations of the beta-catenin gene in mouse colon tumors induced by azoxymethane. Carcinogenesis 21:1117–1120. http://dx.doi.org/10.1093/carcin/21.6.1117.
   PubMedGoogle Scholar
• Jamieson T, Clarke M, Steele CW, Samuel MS, Neumann J, Jung A, Huels D, Olson MF, Das S, Nibbs RJ, Sansom OJ. 2012. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J. Clin. Invest. 122:3127–3144. http://dx.doi.org/10.1172/JCI61067.
   PubMed Web of Science ®Google Scholar
• Rosenberg JM, Welch JP. 1985. Carcinoid tumors of the colon. A study of 72 patients. Am. J. Surg. 149:775–779.
   PubMedGoogle Scholar
• Chawengsaksophak K, James R, Hammond VE, Kontgen F, Beck F. 1997. Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 386:84–87. http://dx.doi.org/10.1038/386084a0.
   PubMedGoogle Scholar
• Aoki K, Tamai Y, Horiike S, Oshima M, Taketo MM. 2003. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/− compound mutant mice. Nat. Genet. 35:323–330. http://dx.doi.org/10.1038/ng1265.
   PubMed Web of Science ®Google Scholar
• Taketo MM. 2006. Mouse models of gastrointestinal tumors. Cancer Sci. 97:355–361. http://dx.doi.org/10.1111/j.1349-7006.2006.00190.x.
   PubMed Web of Science ®Google Scholar
• Prochownik EV. 2004. c-Myc as a therapeutic target in cancer. Expert Rev. Anticancer Ther. 4:289–302. http://dx.doi.org/10.1586/14737140.4.2.289.
   PubMedGoogle Scholar
• Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS. 2011. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146:904–917. http://dx.doi.org/10.1016/j.cell.2011.08.017.
   PubMed Web of Science ®Google Scholar
• Zirath H, Frenzel A, Oliynyk G, Segerstrom L, Westermark UK, Larsson K, Munksgaard Persson M, Hultenby K, Lehtio J, Einvik C, Pahlman S, Kogner P, Jakobsson PJ, Arsenian Henriksson M. 2013. MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells. Proc. Natl. Acad. Sci. U. S. A. 110:10258–10263. http://dx.doi.org/10.1073/pnas.1222404110.
   PubMedGoogle Scholar
• Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE. 2010. Selective inhibition of BET bromodomains. Nature 468:1067–1073. http://dx.doi.org/10.1038/nature09504.
   PubMed Web of Science ®Google Scholar
• Hammoudeh DI, Follis AV, Prochownik EV, Metallo SJ. 2009. Multiple independent binding sites for small-molecule inhibitors on the oncoprotein c-Myc. J. Am. Chem. Soc. 131:7390–7401. http://dx.doi.org/10.1021/ja900616b.
   PubMed Web of Science ®Google Scholar
• Wang H, Hammoudeh DI, Follis AV, Reese BE, Lazo JS, Metallo SJ, Prochownik EV. 2007. Improved low molecular weight Myc-Max inhibitors. Mol. Cancer Ther. 6:2399–2408. http://dx.doi.org/10.1158/1535-7163.MCT-07-0005.
   PubMed Web of Science ®Google Scholar