FXR Regulates Intestinal Cancer Stem Cell Proliferation

Cell

Volumn 176, Issue 5, 2019, Pages 1098-1112.e18

  Fu, Ting ^a   Coulter, Sally ^b   Yoshihara, Eiji ^a   Oh, Tae Gyu ^a   Fang, Sungsoon ^c   Cayabyab, Fritz ^a   Zhu, Qiyun ^d   Zhang, Tong ^a   Leblanc, Mathias ^a   Liu, Sihao ^a   He, Mingxiao ^a   Waizenegger, Wanda ^a   Gasser, Emanuel ^a   Schnabl, Bernd ^e   Atkins, Annette R ^a   Yu, Ruth T ^a   Knight, Rob ^d,f   Liddle, Christopher ^b   Downes, Michael ^a   Evans, Ronald M ^a,g  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b UNIVERSITY OF SYDNEY   (Australia)

^c Yonsei University College of Medicine   (South Korea)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

BA FXR axis; colon cancer progression; genetic and dietary risk factors; Lgr5+ intestinal stem cells

Indexed keywords

BILE ACID; DEOXYCHOLIC ACID; FARNESOID X RECEPTOR; TAURO BETA MURICHOLIC ACID; UNCLASSIFIED DRUG; CELL RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR; TAUROCHOLIC ACID; TAUROMURICHOLIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER GROWTH; CANCER STEM CELL; CELL EXPANSION; CELL GROWTH; CELL PROLIFERATION; COLORECTAL CANCER; CONTROLLED STUDY; DNA DAMAGE; DOWN REGULATION; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME REGULATION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; WNT SIGNALING; ANIMAL; C57BL MOUSE; CELL LINE; COLORECTAL TUMOR; GENE EXPRESSION REGULATION; GENETICS; INTESTINE; INTESTINE TUMOR; LIVER; METABOLISM; ORGANOID; PHYSIOLOGY; RISK FACTOR; SIGNAL TRANSDUCTION;

ANIMALS; BILE ACIDS AND SALTS; CELL LINE; CELL PROLIFERATION; COLORECTAL NEOPLASMS; DEOXYCHOLIC ACID; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTESTINAL NEOPLASMS; INTESTINES; LIVER; MICE; MICE, INBRED C57BL; NEOPLASTIC STEM CELLS; ORGANOIDS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RISK FACTORS; SIGNAL TRANSDUCTION; TAUROCHOLIC ACID; WNT SIGNALING PATHWAY;

EID: 85061095007     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2019.01.036     Document Type: Article

References (57)

1. Aguirre-Gamboa, R., Gomez-Rueda, H., Martínez-Ledesma, E., Martínez-Torteya, A., Chacolla-Huaringa, R., Rodriguez-Barrientos, A., Tamez-Peña, J.G., Treviño, V., SurvExpress: an online biomarker validation tool and database for cancer gene expression data using survival analysis. PLoS ONE, 8, 2013, e74250.
2. Anakk, S., Watanabe, M., Ochsner, S.A., McKenna, N.J., Finegold, M.J., Moore, D.D., Combined deletion of Fxr and Shp in mice induces Cyp17a1 and results in juvenile onset cholestasis. J. Clin. Invest. 121 (2011), 86–95.
3. Barker, N., Ridgway, R.A., van Es, J.H., van de Wetering, M., Begthel, H., van den Born, M., Danenberg, E., Clarke, A.R., Sansom, O.J., Clevers, H., Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457 (2009), 608–611.
4. Bayerdörffer, E., Mannes, G.A., Ochsenkühn, T., Dirschedl, P., Wiebecke, B., Paumgartner, G., Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut 36 (1995), 268–273.
5. Beyaz, S., Mana, M.D., Roper, J., Kedrin, D., Saadatpour, A., Hong, S.J., Bauer-Rowe, K.E., Xifaras, M.E., Akkad, A., Arias, E., et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531 (2016), 53–58.
6. Boivin, G.P., Washington, K., Yang, K., Ward, J.M., Pretlow, T.P., Russell, R., Besselsen, D.G., Godfrey, V.L., Doetschman, T., Dove, W.F., et al. Pathology of mouse models of intestinal cancer: consensus report and recommendations. Gastroenterology 124 (2003), 762–777.
7. Caporaso, J.G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F.D., Costello, E.K., Fierer, N., Peña, A.G., Goodrich, J.K., Gordon, J.I., et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7 (2010), 335–336.
8. Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P.S., Rothenberg, M.E., Leyrat, A.A., Sim, S., Okamoto, J., Johnston, D.M., Qian, D., et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat. Biotechnol. 29 (2011), 1120–1127.
9. de Aguiar Vallim, T.Q., Tarling, E.J., Edwards, P.A., Pleiotropic roles of bile acids in metabolism. Cell Metab. 17 (2013), 657–669.
10. De Gottardi, A., Touri, F., Maurer, C.A., Perez, A., Maurhofer, O., Ventre, G., Bentzen, C.L., Niesor, E.J., Dufour, J.F., The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer. Dig. Dis. Sci. 49 (2004), 982–989.
11. De Magalhaes Filho, C.D., Downes, M., Evans, R., Bile acid analog intercepts liver fibrosis. Cell, 166, 2016, 789.
12. Degirolamo, C., Modica, S., Palasciano, G., Moschetta, A., Bile acids and colon cancer: Solving the puzzle with nuclear receptors. Trends Mol. Med. 17 (2011), 564–572.
13. Devkota, S., Wang, Y., Musch, M.W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D.A., Jabri, B., Chang, E.B., Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487 (2012), 104–108.
14. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., Gingeras, T.R., STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 (2013), 15–21.
15. Dow, L.E., O'Rourke, K.P., Simon, J., Tschaharganeh, D.F., van Es, J.H., Clevers, H., Lowe, S.W., Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 161 (2015), 1539–1552.
16. Downes, M., Liddle, C., Look who's talking: nuclear receptors in the liver and gastrointestinal tract. Cell Metab. 7 (2008), 195–199.
17. Downes, M., Verdecia, M.A., Roecker, A.J., Hughes, R., Hogenesch, J.B., Kast-Woelbern, H.R., Bowman, M.E., Ferrer, J.L., Anisfeld, A.M., Edwards, P.A., et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol. Cell 11 (2003), 1079–1092.
18. Drost, J., van Jaarsveld, R.H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R.M., Offerhaus, G.J., Begthel, H., et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521 (2015), 43–47.
19. Fang, S., Suh, J.M., Reilly, S.M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat. Med. 21 (2015), 159–165.
20. Fodde, R., Smits, R., Clevers, H., APC, signal transduction and genetic instability in colorectal cancer. Nat. Rev. Cancer 1 (2001), 55–67.
21. Font-Burgada, J., Sun, B., Karin, M., Obesity and cancer: the oil that feeds the flame. Cell Metab. 23 (2016), 48–62.
22. Forman, B.M., Goode, E., Chen, J., Oro, A.E., Bradley, D.J., Perlmann, T., Noonan, D.J., Burka, L.T., McMorris, T., Lamph, W.W., et al. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81 (1995), 687–693.
23. Fu, T., Choi, S.-E., Kim, D.-H., Seok, S., Suino-Powell, K.M., Xu, H.E., Kemper, J.K., Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-klotho. Proc. Natl. Acad. Sci. USA 109 (2012), 16137–16142.
24. Fu, T., Kim, Y.C., Byun, S., Kim, D.H., Seok, S., Suino-Powell, K., Xu, H.E., Kemper, B., Kemper, J.K., FXR primes the liver for intestinal FGF15 signaling by transient induction of β-Klotho. Mol. Endocrinol. 30 (2016), 92–103.
25. Fu, T., Zhao, X., Evans, R.M., Liver cancer checks in when bile acid clocks out. Cancer Cell 30 (2016), 827–828.
26. Gregorieff, A., Liu, Y., Inanlou, M.R., Khomchuk, Y., Wrana, J.L., Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature 526 (2015), 715–718.
27. Haber, A.L., Biton, M., Rogel, N., Herbst, R.H., Shekhar, K., Smillie, C., Burgin, G., Delorey, T.M., Howitt, M.R., Katz, Y., et al. A single-cell survey of the small intestinal epithelium. Nature 551 (2017), 333–339.
28. Imray, C.H., Radley, S., Davis, A., Barker, G., Hendrickse, C.W., Donovan, I.A., Lawson, A.M., Baker, P.R., Neoptolemos, J.P., Faecal unconjugated bile acids in patients with colorectal cancer or polyps. Gut 33 (1992), 1239–1245.
29. Kakiyama, G., Muto, A., Takei, H., Nittono, H., Murai, T., Kurosawa, T., Hofmann, A.F., Pandak, W.M., Bajaj, J.S., A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS. J. Lipid Res. 55 (2014), 978–990.
30. Kuipers, E.J., Grady, W.M., Lieberman, D., Seufferlein, T., Sung, J.J., Boelens, P.G., van de Velde, C.J., Watanabe, T., Colorectal cancer. Nat. Rev. Dis. Primers, 1, 2015, 15065.
31. Leng, N., Dawson, J.A., Thomson, J.A., Ruotti, V., Rissman, A.I., Smits, B.M., Haag, J.D., Gould, M.N., Stewart, R.M., Kendziorski, C., EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments. Bioinformatics 29 (2013), 1035–1043.
32. Li, B., Dewey, C.N., RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics, 12, 2011, 323.
33. Mahmoud, N.N., Dannenberg, A.J., Bilinski, R.T., Mestre, J.R., Chadburn, A., Churchill, M., Martucci, C., Bertagnolli, M.M., Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis. Carcinogenesis 20 (1999), 299–303.
34. Makishima, M., Okamoto, A.Y., Repa, J.J., Tu, H., Learned, R.M., Luk, A., Hull, M.V., Lustig, K.D., Mangelsdorf, D.J., Shan, B., Identification of a nuclear receptor for bile acids. Science 284 (1999), 1362–1365.
35. Maran, R.R., Thomas, A., Roth, M., Sheng, Z., Esterly, N., Pinson, D., Gao, X., Zhang, Y., Ganapathy, V., Gonzalez, F.J., Guo, G.L., Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J. Pharmacol. Exp. Ther. 328 (2009), 469–477.
36. Modica, S., Murzilli, S., Salvatore, L., Schmidt, D.R., Moschetta, A., Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res. 68 (2008), 9589–9594.
37. Ongen, H., Andersen, C.L., Bramsen, J.B., Oster, B., Rasmussen, M.H., Ferreira, P.G., Sandoval, J., Vidal, E., Whiffin, N., Planchon, A., et al. Putative cis-regulatory drivers in colorectal cancer. Nature 512 (2014), 87–90.
38. Pai, R., Tarnawski, A.S., Tran, T., Deoxycholic acid activates beta-catenin signaling pathway and increases colon cell cancer growth and invasiveness. Mol. Biol. Cell 15 (2004), 2156–2163.
39. Parks, D.J., Blanchard, S.G., Bledsoe, R.K., Chandra, G., Consler, T.G., Kliewer, S.A., Stimmel, J.B., Willson, T.M., Zavacki, A.M., Moore, D.D., Lehmann, J.M., Bile acids: natural ligands for an orphan nuclear receptor. Science 284 (1999), 1365–1368.
40. Parséus, A., Sommer, N., Sommer, F., Caesar, R., Molinaro, A., Ståhlman, M., Greiner, T.U., Perkins, R., Bäckhed, F., Microbiota-induced obesity requires farnesoid X receptor. Gut 66 (2017), 429–437.
41. Powell, S.M., Zilz, N., Beazer-Barclay, Y., Bryan, T.M., Hamilton, S.R., Thibodeau, S.N., Vogelstein, B., Kinzler, K.W., APC mutations occur early during colorectal tumorigenesis. Nature 359 (1992), 235–237.
42. Rajagopalan, H., Nowak, M.A., Vogelstein, B., Lengauer, C., The significance of unstable chromosomes in colorectal cancer. Nat. Rev. Cancer 3 (2003), 695–701.
43. Rodríguez-Colman, M.J., Schewe, M., Meerlo, M., Stigter, E., Gerrits, J., Pras-Raves, M., Sacchetti, A., Hornsveld, M., Oost, K.C., Snippert, H.J., et al. Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature 543 (2017), 424–427.
44. Sato, T., Clevers, H., Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340 (2013), 1190–1194.
45. Sato, T., Vries, R.G., Snippert, H.J., van de Wetering, M., Barker, N., Stange, D.E., van Es, J.H., Abo, A., Kujala, P., Peters, P.J., Clevers, H., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459 (2009), 262–265.
46. Sato, T., van Es, J.H., Snippert, H.J., Stange, D.E., Vries, R.G., van den Born, M., Barker, N., Shroyer, N.F., van de Wetering, M., Clevers, H., Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469 (2011), 415–418.
47. Sayin, S.I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., Bäckhed, F., Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17 (2013), 225–235.
48. Schuijers, J., Junker, J.P., Mokry, M., Hatzis, P., Koo, B.K., Sasselli, V., van der Flier, L.G., Cuppen, E., van Oudenaarden, A., Clevers, H., Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in intestinal crypts. Cell Stem Cell 16 (2015), 158–170.
49. Selmin, O.I., Fang, C., Lyon, A.M., Doetschman, T.C., Thompson, P.A., Martinez, J.D., Smith, J.W., Lance, P.M., Romagnolo, D.F., Inactivation of adenomatous polyposis coli reduces bile acid/farnesoid X receptor expression through Fxr gene CpG methylation in mouse colon tumors and human colon cancer cells. J. Nutr. 146 (2016), 236–242.
50. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., Mesirov, J.P., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102 (2005), 15545–15550.
51. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., Schoonjans, K., Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7 (2008), 678–693.
52. Tomasetti, C., Vogelstein, B., Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347 (2015), 78–81.
53. Tomasetti, C., Li, L., Vogelstein, B., Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355 (2017), 1330–1334.
54. van der Flier, L.G., Haegebarth, A., Stange, D.E., van de Wetering, M., Clevers, H., OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137 (2009), 15–17.
55. van der Flier, L.G., van Gijn, M.E., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D.E., Begthel, H., van den Born, M., Guryev, V., Oving, I., et al. Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell 136 (2009), 903–912.
56. Wang, K., Kim, M.K., Di Caro, G., Wong, J., Shalapour, S., Wan, J., Zhang, W., Zhong, Z., Sanchez-Lopez, E., Wu, L.W., et al. Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity 41 (2014), 1052–1063.
57. Washington, M.K., Powell, A.E., Sullivan, R., Sundberg, J.P., Wright, N., Coffey, R.J., Dove, W.F., Pathology of rodent models of intestinal cancer: progress report and recommendations. Gastroenterology 144 (2013), 705–717.