Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis

Cell

Volumn 170, Issue 5, 2017, Pages 875-888.e20

  Roe, Jae Seok ^a   Hwang, Chang Il ^a,b   Somerville, Tim D D ^a   Milazzo, Joseph P ^a   Lee, Eun Jung ^a,b   Da Silva, Brandon ^a,b   Maiorino, Laura ^a   Tiriac, Hervé ^a,b   Young, C Megan ^a,b   Miyabayashi, Koji ^a,b   Filippini, Dea ^a,b   Creighton, Brianna ^a,b   Burkhart, Richard A ^c   Buscaglia, Jonathan M ^d   Kim, Edward J ^e   Grem, Jean L ^f   Lazenby, Audrey J ^f   Grunkemeyer, James A ^g   Hollingsworth, Michael A ^g   Grandgenett, Paul M ^g   Egeblad, Mikala ^a   Park, Youngkyu ^a,b   Tuveson, David A ^a,b   Vakoc, Christopher R ^a   more..

^a Simons Center for Quantitative Biology   (United States)

^b Lustgarten Foundation Pancreatic Cancer Laboratory at Cold Spring Harbor   (United States)

^c JOHNS HOPKINS HOSPITAL   (United States)

^d STONY BROOK UNIVERSITY   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^g UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

enhancer; FOXA1; metastasis; organoid; pancreatic cancer; pancreatic ductal adenocarcinoma

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 3ALPHA; FOXA1 PROTEIN, HUMAN; FOXA1 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; ENHANCER LANDSCAPE; ENHANCER REGION; EPIGENETICS; FEMALE; GENE EXPRESSION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOUSE; MOUSE MODEL; NONHUMAN; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; PROTEIN FUNCTION; UPREGULATION; ADENOCARCINOMA; ANIMAL; C57BL MOUSE; CYTOPLASM; DISEASE MODEL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; METASTASIS; PANCREAS; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; TUMOR CELL LINE;

ADENOCARCINOMA; ANIMALS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; ENHANCER ELEMENTS, GENETIC; EPIGENOMICS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPATOCYTE NUCLEAR FACTOR 3-ALPHA; HUMANS; MALE; MICE; MICE, INBRED C57BL; NEOPLASM METASTASIS; ORGANOIDS; PANCREAS; PANCREATIC NEOPLASMS;

EID: 85026197846     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2017.07.007     Document Type: Article

References (62)

1. Abraham, B.J., Hnisz, D., Weintraub, A.S., Kwiatkowski, N., Li, C.H., Li, Z., Weichert-Leahey, N., Rahman, S., Liu, Y., Etchin, J., et al. Small genomic insertions form enhancers that misregulate oncogenes. Nat. Commun., 8, 2017, 14385.
2. Arda, H.E., Li, L., Tsai, J., Torre, E.A., Rosli, Y., Peiris, H., Spitale, R.C., Dai, C., Gu, X., Qu, K., et al. Age-dependent pancreatic gene regulation reveals mechanisms governing human beta cell function. Cell Metab. 23 (2016), 909–920.
3. Bailey, P., Chang, D.K., Nones, K., Johns, A.L., Patch, A.M., Gingras, M.C., Miller, D.K., Christ, A.N., Bruxner, T.J., Quinn, M.C., et al., Australian Pancreatic Cancer Genome Initiative. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531 (2016), 47–52.
4. Boj, S.F., Hwang, C.I., Baker, L.A., Chio, I.I., Engle, D.D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M.S., et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160 (2015), 324–338.
5. Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y., Greenleaf, W.J., Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10 (2013), 1213–1218.
6. Campbell, P.J., Yachida, S., Mudie, L.J., Stephens, P.J., Pleasance, E.D., Stebbings, L.A., Morsberger, L.A., Latimer, C., McLaren, S., Lin, M.L., et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467 (2010), 1109–1113.
7. Chio, I.I., Jafarnejad, S.M., Ponz-Sarvise, M., Park, Y., Rivera, K., Palm, W., Wilson, J., Sangar, V., Hao, Y., Öhlund, D., et al. NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer. Cell 166 (2016), 963–976.
8. Christensen, C.L., Kwiatkowski, N., Abraham, B.J., Carretero, J., Al-Shahrour, F., Zhang, T., Chipumuro, E., Herter-Sprie, G.S., Akbay, E.A., Altabef, A., et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell 26 (2014), 909–922.
9. Collisson, E.A., Sadanandam, A., Olson, P., Gibb, W.J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G.E., Jakkula, L., et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 17 (2011), 500–503.
10. Denny, S.K., Yang, D., Chuang, C.H., Brady, J.J., Lim, J.S., Grüner, B.M., Chiou, S.H., Schep, A.N., Baral, J., Hamard, C., et al. Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. Cell 166 (2016), 328–342.
11. Diaferia, G.R., Balestrieri, C., Prosperini, E., Nicoli, P., Spaggiari, P., Zerbi, A., Natoli, G., Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer. EMBO J. 35 (2016), 595–617.
12. Fellmann, C., Hoffmann, T., Sridhar, V., Hopfgartner, B., Muhar, M., Roth, M., Lai, D.Y., Barbosa, I.A., Kwon, J.S., Guan, Y., et al. An optimized microRNA backbone for effective single-copy RNAi. Cell Rep. 5 (2013), 1704–1713.
13. Gao, N., LeLay, J., Vatamaniuk, M.Z., Rieck, S., Friedman, J.R., Kaestner, K.H., Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev. 22 (2008), 3435–3448.
14. Guerra, C., Barbacid, M., Genetically engineered mouse models of pancreatic adenocarcinoma. Mol. Oncol. 7 (2013), 232–247.
15. Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H., Glass, C.K., Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38 (2010), 576–589.
16. Hessmann, E., Johnsen, S.A., Siveke, J.T., Ellenrieder, V., Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon?. Gut 66 (2017), 168–179.
17. Hingorani, S.R., Wang, L., Multani, A.S., Combs, C., Deramaudt, T.B., Hruban, R.H., Rustgi, A.K., Chang, S., Tuveson, D.A., Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7 (2005), 469–483.
18. Hruban, R.H., Goggins, M., Parsons, J., Kern, S.E., Progression model for pancreatic cancer. Clin. Cancer Res. 6 (2000), 2969–2972.
19. Kong, S.L., Li, G., Loh, S.L., Sung, W.K., Liu, E.T., Cellular reprogramming by the conjoint action of ERα, FOXA1, and GATA3 to a ligand-inducible growth state. Mol. Syst. Biol., 7, 2011, 526.
20. Krebs, A.M., Mitschke, J., Lasierra Losada, M., Schmalhofer, O., Boerries, M., Busch, H., Boettcher, M., Mougiakakos, D., Reichardt, W., Bronsert, P., et al. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat. Cell Biol. 19 (2017), 518–529.
21. Kugel, S., Sebastián, C., Fitamant, J., Ross, K.N., Saha, S.K., Jain, E., Gladden, A., Arora, K.S., Kato, Y., Rivera, M.N., et al. SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. Cell 165 (2016), 1401–1415.
22. Langmead, B., Trapnell, C., Pop, M., Salzberg, S.L., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol., 10, 2009, R25.
23. Larsen, H.L., Grapin-Botton, A., The molecular and morphogenetic basis of pancreas organogenesis. Semin. Cell Dev. Biol. 66 (2017), 51–68.
24. Levine, A.J., Greenbaum, B., The maintenance of epigenetic states by p53: the guardian of the epigenome. Oncotarget 3 (2012), 1503–1504.
25. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
26. Lin, C.Y., Lovén, J., Rahl, P.B., Paranal, R.M., Burge, C.B., Bradner, J.E., Lee, T.I., Young, R.A., Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151 (2012), 56–67.
27. Loh, K.M., Ang, L.T., Zhang, J., Kumar, V., Ang, J., Auyeong, J.Q., Lee, K.L., Choo, S.H., Lim, C.Y., Nichane, M., et al. Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations. Cell Stem Cell 14 (2014), 237–252.
28. Long, H.K., Prescott, S.L., Wysocka, J., Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution. Cell 167 (2016), 1170–1187.
29. Makohon-Moore, A.P., Zhang, M., Reiter, J.G., Bozic, I., Allen, B., Kundu, D., Chatterjee, K., Wong, F., Jiao, Y., Kohutek, Z.A., et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nat. Genet. 49 (2017), 358–366.
30. McDonald, O.G., Li, X., Saunders, T., Tryggvadottir, R., Mentch, S.J., Warmoes, M.O., Word, A.E., Carrer, A., Salz, T.H., Natsume, S., et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat. Genet. 49 (2017), 367–376.
31. McLean, C.Y., Bristor, D., Hiller, M., Clarke, S.L., Schaar, B.T., Lowe, C.B., Wenger, A.M., Bejerano, G., GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28 (2010), 495–501.
32. Mihara, E., Hirai, H., Yamamoto, H., Tamura-Kawakami, K., Matano, M., Kikuchi, A., Sato, T., Takagi, J., Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. eLife, 5, 2016, e11621.
33. Moffitt, R.A., Marayati, R., Flate, E.L., Volmar, K.E., Loeza, S.G., Hoadley, K.A., Rashid, N.U., Williams, L.A., Eaton, S.C., Chung, A.H., et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat. Genet. 47 (2015), 1168–1178.
34. Muzumdar, M.D., Dorans, K.J., Chung, K.M., Robbins, R., Tammela, T., Gocheva, V., Li, C.M., Jacks, T., Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Nat. Commun., 7, 2016, 12685.
35. Neureiter, D., Jäger, T., Ocker, M., Kiesslich, T., Epigenetics and pancreatic cancer: pathophysiology and novel treatment aspects. World J. Gastroenterol. 20 (2014), 7830–7848.
36. Öhlund, D., Elyada, E., Tuveson, D., Fibroblast heterogeneity in the cancer wound. J. Exp. Med. 211 (2014), 1503–1523.
37. Olive, K.P., Tuveson, D.A., Ruhe, Z.C., Yin, B., Willis, N.A., Bronson, R.T., Crowley, D., Jacks, T., Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119 (2004), 847–860.
38. Quinlan, A.R., Hall, I.M., BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26 (2010), 841–842.
39. Ryan, D.P., Hong, T.S., Bardeesy, N., Pancreatic adenocarcinoma. N. Engl. J. Med. 371 (2014), 1039–1049.
40. Sakai, Y., Yanagisawa, A., Shimada, M., Hidaka, E., Seki, M., Tada, Y., Harada, T., Saisho, H., Kato, Y., K-ras gene mutations and loss of heterozygosity at the p53 gene locus relative to histological characteristics of mucin-producing tumors of the pancreas. Hum. Pathol. 31 (2000), 795–803.
41. Sekiya, S., Suzuki, A., Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475 (2011), 390–393.
42. Shi, J., Wang, E., Milazzo, J.P., Wang, Z., Kinney, J.B., Vakoc, C.R., Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat. Biotechnol. 33 (2015), 661–667.
43. Siegel, R.L., Miller, K.D., Jemal, A., Cancer Statistics, 2017. CA Cancer J. Clin. 67 (2017), 7–30.
44. Soares, K.C., Foley, K., Olino, K., Leubner, A., Mayo, S.C., Jain, A., Jaffee, E., Schulick, R.D., Yoshimura, K., Edil, B., Zheng, L., A preclinical murine model of hepatic metastases. J. Vis. Exp., 91, 2014, 51677.
45. Song, Y., Washington, M.K., Crawford, H.C., Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res. 70 (2010), 2115–2125.
46. Spitz, F., Furlong, E.E., Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13 (2012), 613–626.
47. Stelnicki, E.J., Arbeit, J., Cass, D.L., Saner, C., Harrison, M., Largman, C., Modulation of the human homeobox genes PRX-2 and HOXB13 in scarless fetal wounds. J. Invest. Dermatol. 111 (1998), 57–63.
48. Thomas-Chollier, M., Hufton, A., Heinig, M., O'Keeffe, S., Masri, N.E., Roider, H.G., Manke, T., Vingron, M., Transcription factor binding predictions using TRAP for the analysis of ChIP-seq data and regulatory SNPs. Nat. Protoc. 6 (2011), 1860–1869.
49. Trapnell, C., Pachter, L., Salzberg, S.L., TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25 (2009), 1105–1111.
50. Trapnell, C., Williams, B.A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M.J., Salzberg, S.L., Wold, B.J., Pachter, L., Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28 (2010), 511–515.
51. Tripathi, S., Pohl, M.O., Zhou, Y., Rodriguez-Frandsen, A., Wang, G., Stein, D.A., Moulton, H.M., DeJesus, P., Che, J., Mulder, L.C., et al. Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding. Cell Host Microbe 18 (2015), 723–735.
52. Vigil, D., Martin, T.D., Williams, F., Yeh, J.J., Campbell, S.L., Der, C.J., Aberrant overexpression of the Rgl2 Ral small GTPase-specific guanine nucleotide exchange factor promotes pancreatic cancer growth through Ral-dependent and Ral-independent mechanisms. J. Biol. Chem. 285 (2010), 34729–34740.
53. Waddell, N., Pajic, M., Patch, A.M., Chang, D.K., Kassahn, K.S., Bailey, P., Johns, A.L., Miller, D., Nones, K., Quek, K., et al., Australian Pancreatic Cancer Genome Initiative. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518 (2015), 495–501.
54. Weissmueller, S., Manchado, E., Saborowski, M., Morris, J.P. 4th, Wagenblast, E., Davis, C.A., Moon, S.H., Pfister, N.T., Tschaharganeh, D.F., Kitzing, T., et al. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling. Cell 157 (2014), 382–394.
55. Whittle, M.C., Izeradjene, K., Rani, P.G., Feng, L., Carlson, M.A., DelGiorno, K.E., Wood, L.D., Goggins, M., Hruban, R.H., Chang, A.E., et al. RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma. Cell 161 (2015), 1345–1360.
56. Xie, R., Everett, L.J., Lim, H.W., Patel, N.A., Schug, J., Kroon, E., Kelly, O.G., Wang, A., D'Amour, K.A., Robins, A.J., et al. Dynamic chromatin remodeling mediated by polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells. Cell Stem Cell 12 (2013), 224–237.
57. Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R.H., Eshleman, J.R., Nowak, M.A., et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467 (2010), 1114–1117.
58. Yamano, M., Fujii, H., Takagaki, T., Kadowaki, N., Watanabe, H., Shirai, T., Genetic progression and divergence in pancreatic carcinoma. Am. J. Pathol. 156 (2000), 2123–2133.
59. Ye, X., Weinberg, R.A., Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression. Trends Cell Biol. 25 (2015), 675–686.
60. Yue, F., Cheng, Y., Breschi, A., Vierstra, J., Wu, W., Ryba, T., Sandstrom, R., Ma, Z., Davis, C., Pope, B.D., et al., Mouse ENCODE Consortium. A comparative encyclopedia of DNA elements in the mouse genome. Nature 515 (2014), 355–364.
61. Zaret, K.S., Lerner, J., Iwafuchi-Doi, M., Chromatin Scanning by Dynamic Binding of Pioneer Factors. Mol. Cell 62 (2016), 665–667.
62. Zentner, G.E., Scacheri, P.C., The chromatin fingerprint of gene enhancer elements. J. Biol. Chem. 287 (2012), 30888–30896.