1932

Abstract

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal of cellular waste in nutrient-poor environments. Intestinal stem cells (ISCs), the primary cell of origin for CRCs, must adapt their metabolism along the adenoma-carcinoma sequence to the unique features of their complex microenvironment that include interactions with intestinal epithelial cells, immune cells, stromal cells, commensal microbes, and dietary components. Emerging evidence implicates modifiable risk factors related to the environment, such as diet, as important in CRC pathogenesis. Here, we focus on describing the metabolism of ISCs, diets that influence CRC initiation, CRC genetics and metabolism, and the tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, and the tumor microenvironment in enhancing or supporting CRC tumorigenesis are becoming better understood. Thus, greater knowledge of CRC metabolism holds promise for improved prevention and treatment.

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2023-01-24
2024-03-28
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Literature Cited

  1. 1.
    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I et al. 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71:209–49
    [Google Scholar]
  2. 2.
    Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA et al. 2018. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J. Clin. 68:31–54
    [Google Scholar]
  3. 3.
    Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF et al. 2020. Colorectal cancer statistics, 2020. CA Cancer J. Clin. 70:145–64
    [Google Scholar]
  4. 4.
    Fearon ER, Vogelstein B. 1990. A genetic model for colorectal tumorigenesis. Cell 61:759–67
    [Google Scholar]
  5. 5.
    Paterson C, Clevers H, Bozic I. 2020. Mathematical model of colorectal cancer initiation. PNAS 117:20681–88
    [Google Scholar]
  6. 6.
    Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A et al. 2015. The consensus molecular subtypes of colorectal cancer. Nat. Med. 21:1350–56
    [Google Scholar]
  7. 7.
    Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J. Gen. Physiol. 8:519–30
    [Google Scholar]
  8. 8.
    DeBerardinis RJ, Chandel NS. 2016. Fundamentals of cancer metabolism. Sci. Adv. 2:e1600200
    [Google Scholar]
  9. 9.
    Fantin VR, St-Pierre J, Leder P. 2006. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9:425–34
    [Google Scholar]
  10. 10.
    Lunt SY, Vander Heiden MG. 2011. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27:441–64
    [Google Scholar]
  11. 11.
    Pavlova NN, Zhu J, Thompson CB. 2022. The hallmarks of cancer metabolism: still emerging. Cell Metab. 34:355–77
    [Google Scholar]
  12. 12.
    Helander HF, Fandriks L. 2014. Surface area of the digestive tract—revisited. Scand. J. Gastroenterol. 49:681–89
    [Google Scholar]
  13. 13.
    Kiela PR, Ghishan FK. 2016. Physiology of intestinal absorption and secretion. Best Pract. Res. Clin. Gastroenterol. 30:145–59
    [Google Scholar]
  14. 14.
    Sandle GI. 1998. Salt and water absorption in the human colon: a modern appraisal. Gut 43:294–99
    [Google Scholar]
  15. 15.
    Sender R, Fuchs S, Milo R 2016. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 14:e1002533
    [Google Scholar]
  16. 16.
    Barker N, van Es JH, Kuipers J, Kujala P, van den Born M et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–7
    [Google Scholar]
  17. 17.
    Pinto D, Gregorieff A, Begthel H, Clevers H. 2003. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 17:1709–13
    [Google Scholar]
  18. 18.
    Kim KA, Kakitani M, Zhao J, Oshima T, Tang T et al. 2005. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309:1256–59
    [Google Scholar]
  19. 19.
    Kosinski C, Li VS, Chan AS, Zhang J, Ho C et al. 2007. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. PNAS 104:15418–23
    [Google Scholar]
  20. 20.
    Lueschow SR, McElroy SJ. 2020. The Paneth cell: the curator and defender of the immature small intestine. Front. Immunol. 11:587
    [Google Scholar]
  21. 21.
    Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG et al. 2011. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–18
    [Google Scholar]
  22. 22.
    Sasaki N, Sachs N, Wiebrands K, Ellenbroek SI, Fumagalli A et al. 2016. Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon. PNAS 113:E5399–407
    [Google Scholar]
  23. 23.
    Degirmenci B, Valenta T, Dimitrieva S, Hausmann G, Basler K. 2018. GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature 558:449–53
    [Google Scholar]
  24. 24.
    Shoshkes-Carmel M, Wang YJ, Wangensteen KJ, Toth B, Kondo A et al. 2018. Subepithelial telocytes are an important source of Wnts that supports intestinal crypts. Nature 557:242–46
    [Google Scholar]
  25. 25.
    Gehart H, Clevers H. 2019. Tales from the crypt: new insights into intestinal stem cells. Nat. Rev. Gastroenterol. Hepatol. 16:19–34
    [Google Scholar]
  26. 26.
    Stringari C, Edwards RA, Pate KT, Waterman ML, Donovan PJ, Gratton E. 2012. Metabolic trajectory of cellular differentiation in small intestine by phasor fluorescence lifetime microscopy of NADH. Sci. Rep. 2:568
    [Google Scholar]
  27. 27.
    Durand A, Donahue B, Peignon G, Letourneur F, Cagnard N et al. 2012. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). PNAS 109:8965–70
    [Google Scholar]
  28. 28.
    Kim M, Park K. 2018. Dietary fat intake and risk of colorectal cancer: a systematic review and meta-analysis of prospective studies. Nutrients 10:1963
    [Google Scholar]
  29. 29.
    Rodriguez-Colman MJ, Schewe M, Meerlo M, Stigter E, Gerrits J et al. 2017. Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature 543:424–27
    [Google Scholar]
  30. 30.
    Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P et al. 2017. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat. Cell Biol. 19:1027–36
    [Google Scholar]
  31. 31.
    Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A et al. 2012. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science 337:96–100
    [Google Scholar]
  32. 32.
    Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A et al. 2016. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531:53–58
    [Google Scholar]
  33. 33.
    Mana MD, Hussey AM, Tzouanas CN, Imada S, Barrera Millan Y et al. 2021. High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity. Cell Rep. 35:109212
    [Google Scholar]
  34. 34.
    Beyaz S, Chung C, Mou H, Bauer-Rowe KE, Xifaras ME et al. 2021. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell 28:1922–35.e5
    [Google Scholar]
  35. 35.
    Wang B, Rong X, Palladino END, Wang JF, Fogelman AM et al. 2018. Phospholipid remodeling and cholesterol availability regulate intestinal stemness and tumorigenesis. Cell Stem Cell 22:206–220.e4
    [Google Scholar]
  36. 36.
    Wei P, Dove KK, Bensard C, Schell JC, Rutter J. 2018. The force is strong with this one: metabolism (over)powers stem cell fate. Trends Cell Biol. 28:551–59
    [Google Scholar]
  37. 37.
    Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H et al. 2009. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–11
    [Google Scholar]
  38. 38.
    de Lau W, Peng WC, Gros P, Clevers H. 2014. The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength. Genes Dev. 28:305–16
    [Google Scholar]
  39. 39.
    Huels DJ, Sansom OJ. 2015. Stem versus non-stem cell origin of colorectal cancer. Br. J. Cancer 113:1–5
    [Google Scholar]
  40. 40.
    McCarthy N, Kraiczy J, Shivdasani RA. 2020. Cellular and molecular architecture of the intestinal stem cell niche. Nat. Cell Biol. 22:1033–41
    [Google Scholar]
  41. 41.
    McCarthy N, Manieri E, Storm EE, Saadatpour A, Luoma AM et al. 2020. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell 26:391–402.e5
    [Google Scholar]
  42. 42.
    Sullivan BA, Noujaim M, Roper J. 2022. Cause, epidemiology, and histology of polyps and pathways to colorectal cancer. Gastrointest. Endosc. Clin. N. Am. 32:177–94
    [Google Scholar]
  43. 43.
    Karahalios A, English DR, Simpson JA. 2015. Weight change and risk of colorectal cancer: a systematic review and meta-analysis. Am. J. Epidemiol. 181:832–45
    [Google Scholar]
  44. 44.
    Li H-J, Boakye D, Chen X-C, Jansen L, Chang-Claude J et al. 2022. Associations of body mass index at different ages with early-onset colorectal cancer. Gastroenterology 162:1088–97.e3
    [Google Scholar]
  45. 45.
    Fontana L, Partridge L, Longo VD. 2010. Extending healthy life span—from yeast to humans. Science 328:321–26
    [Google Scholar]
  46. 46.
    Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW et al. 2017. Caloric restriction improves health and survival of rhesus monkeys. Nat. Commun. 8:14063
    [Google Scholar]
  47. 47.
    Mai V, Colbert LH, Berrigan D, Perkins SN, Pfeiffer R et al. 2003. Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in ApcMin mice through different mechanisms. Cancer Res. 63:1752–55
    [Google Scholar]
  48. 48.
    Suh Y, Atzmon G, Cho MO, Hwang D, Liu B et al. 2008. Functionally significant insulin-like growth factor I receptor mutations in centenarians. PNAS 105:3438–42
    [Google Scholar]
  49. 49.
    Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A et al. 2003. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–87
    [Google Scholar]
  50. 50.
    Renehan AG, O'Connell J, O'Halloran D, Shanahan F, Potten CS et al. 2003. Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications. Horm. Metab. Res. 35:712–25
    [Google Scholar]
  51. 51.
    Fontana L, Villareal DT, Das SK, Smith SR, Meydani SN et al. 2016. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial. Aging Cell 15:22–27
    [Google Scholar]
  52. 52.
    Pomatto-Watson LCD, Bodogai M, Bosompra O, Kato J, Wong S et al. 2021. Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition. Nat. Commun. 12:6201
    [Google Scholar]
  53. 53.
    Green CL, Lamming DW, Fontana L. 2022. Molecular mechanisms of dietary restriction promoting health and longevity. Nat. Rev. Mol. Cell Biol. 23:56–73
    [Google Scholar]
  54. 54.
    Longo VD, Mattson MP. 2014. Fasting: molecular mechanisms and clinical applications. Cell Metab. 19:181–92
    [Google Scholar]
  55. 55.
    Longo VD, Di Tano M, Mattson MP, Guidi N. 2021. Intermittent and periodic fasting, longevity and disease. Nat. Aging 1:47–59
    [Google Scholar]
  56. 56.
    Cheng CW, Adams GB, Perin L, Wei M, Zhou X et al. 2014. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell 14:810–23
    [Google Scholar]
  57. 57.
    Mihaylova MM, Sabatini DM, Yilmaz OH. 2014. Dietary and metabolic control of stem cell function in physiology and cancer. Cell Stem Cell 14:292–305
    [Google Scholar]
  58. 58.
    Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD et al. 2018. Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem Cell 22:769–78.e4
    [Google Scholar]
  59. 59.
    Bruens L, Ellenbroek SIJ, Suijkerbuijk SJE, Azkanaz M, Hale AJ et al. 2020. Calorie restriction increases the number of competing stem cells and decreases mutation retention in the intestine. Cell Rep. 32:107937
    [Google Scholar]
  60. 60.
    Lien EC, Westermark AM, Zhang Y, Yuan C, Li Z et al. 2021. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature 599:302–7
    [Google Scholar]
  61. 61.
    Weng ML, Chen WK, Chen XY, Lu H, Sun ZR et al. 2020. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression. Nat. Commun. 11:1869
    [Google Scholar]
  62. 62.
    Sun P, Wang H, He Z, Chen X, Wu Q et al. 2017. Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. Oncotarget 8:74649–60
    [Google Scholar]
  63. 63.
    O'Flanagan CH, Smith LA, McDonell SB, Hursting SD. 2017. When less may be more: calorie restriction and response to cancer therapy. BMC Med. 15:106
    [Google Scholar]
  64. 64.
    Nencioni A, Caffa I, Cortellino S, Longo VD. 2018. Fasting and cancer: molecular mechanisms and clinical application. Nat. Rev. Cancer 18:707–19
    [Google Scholar]
  65. 65.
    Castejon M, Plaza A, Martinez-Romero J, Fernandez-Marcos PJ, Cabo R, Diaz-Ruiz A. 2020. Energy restriction and colorectal cancer: a call for additional research. Nutrients 12:114
    [Google Scholar]
  66. 66.
    Tessitore L, Tomasi C, Greco M, Sesca E, Laconi E et al. 1996. A subnecrogenic dose of diethylnitrosamine is able to initiate hepatocarcinogenesis in the rat when coupled with fasting/refeeding. Carcinogenesis 17:289–92
    [Google Scholar]
  67. 67.
    McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M et al. 2019. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. J. Natl. Cancer Inst. 111:158–69
    [Google Scholar]
  68. 68.
    Fuchs MA, Yuan C, Sato K, Niedzwiecki D, Ye X et al. 2017. Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance). Ann. Oncol. 28:1359–67
    [Google Scholar]
  69. 69.
    Zgaga L, Theodoratou E, Farrington SM, Din FV, Ooi LY et al. 2014. Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. J. Clin. Oncol. 32:2430–39
    [Google Scholar]
  70. 70.
    Vaughan-Shaw PG, Buijs LF, Blackmur JP, Theodoratou E, Zgaga L et al. 2020. The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials. Br. J. Cancer 123:1705–12
    [Google Scholar]
  71. 71.
    Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. 2019. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann. Oncol. 30:733–43
    [Google Scholar]
  72. 72.
    Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. 2014. The role of vitamin D in reducing cancer risk and progression. Nat. Rev. Cancer 14:342–57
    [Google Scholar]
  73. 73.
    Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P et al. 2015. Proteomics. Tissue-based map of the human proteome. Science 347:1260419
    [Google Scholar]
  74. 74.
    Fernandez-Barral A, Costales-Carrera A, Buira SP, Jung P, Ferrer-Mayorga G et al. 2020. Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids. FEBS J. 287:53–72
    [Google Scholar]
  75. 75.
    Ngo B, Van Riper JM, Cantley LC, Yun J 2019. Targeting cancer vulnerabilities with high-dose vitamin C. Nat. Rev. Cancer 19:271–82
    [Google Scholar]
  76. 76.
    Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A et al. 2015. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350:1391–96
    [Google Scholar]
  77. 77.
    Magri A, Germano G, Lorenzato A, Lamba S, Chila R et al. 2020. High-dose vitamin C enhances cancer immunotherapy. Sci. Transl. Med. 12:eaay8707
    [Google Scholar]
  78. 78.
    Ferraris RP, Choe JY, Patel CR. 2018. Intestinal absorption of fructose. Annu. Rev. Nutr. 38:41–67
    [Google Scholar]
  79. 79.
    Joh HK, Lee DH, Hur J, Nimptsch K, Chang Y et al. 2021. Simple sugar and sugar-sweetened beverage intake during adolescence and risk of colorectal cancer precursors. Gastroenterology 161:128–42.e20
    [Google Scholar]
  80. 80.
    Taylor SR, Ramsamooj S, Liang RJ, Katti A, Pozovskiy R et al. 2021. Dietary fructose improves intestinal cell survival and nutrient absorption. Nature 597:263–67
    [Google Scholar]
  81. 81.
    Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang SK et al. 2019. High-fructose corn syrup enhances intestinal tumor growth in mice. Science 363:1345–49
    [Google Scholar]
  82. 82.
    Bu P, Chen KY, Xiang K, Johnson C, Crown SB et al. 2018. Aldolase B-mediated fructose metabolism drives metabolic reprogramming of colon cancer liver metastasis. Cell Metab. 27:1249–62.e4
    [Google Scholar]
  83. 83.
    Carreno DV, Corro NB, Cerda-Infante JF, Echeverria CE, Asencio-Barria CA et al. 2021. Dietary fructose promotes prostate cancer growth. Cancer Res. 81:2824–32
    [Google Scholar]
  84. 84.
    Hu S, Wang L, Yang D, Li L, Togo J et al. 2018. Dietary fat, but not protein or carbohydrate, regulates energy intake and causes adiposity in mice. Cell Metab. 28:415–31.e4
    [Google Scholar]
  85. 85.
    Astrup A, Buemann B, Western P, Toubro S, Raben A, Christensen NJ. 1994. Obesity as an adaptation to a high-fat diet: evidence from a cross-sectional study. Am. J. Clin. Nutr. 59:350–55
    [Google Scholar]
  86. 86.
    Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. 2016. Obesity, inflammation, and cancer. Annu. Rev. Pathol. Mech. Dis. 11:421–49
    [Google Scholar]
  87. 87.
    Li X, Jansen L, Chang-Claude J, Hoffmeister M, Brenner H. 2022. Risk of colorectal cancer associated with lifetime excess weight. JAMA Oncol. 8:730–37
    [Google Scholar]
  88. 88.
    Daniel CR, Shu X, Ye Y, Gu J, Raju GS et al. 2016. Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre. Br. J. Cancer 114:103–9
    [Google Scholar]
  89. 89.
    Wiggins T, Antonowicz SS, Markar SR. 2019. Cancer risk following bariatric surgery—systematic review and meta-analysis of national population-based cohort studies. Obes. Surg. 29:1031–39
    [Google Scholar]
  90. 90.
    Stroud AM, Dewey EN, Husain FA, Fischer JM, Courcoulas AP et al. 2020. Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort. Surg. Obes. Relat. Dis. 16:1086–94
    [Google Scholar]
  91. 91.
    Licholai JA, Nguyen KP, Fobbs WC, Schuster CJ, MA Ali, Kravitz AV. 2018. Why do mice overeat high-fat diets? How high-fat diet alters the regulation of daily caloric intake in mice. Obesity 26:1026–33
    [Google Scholar]
  92. 92.
    Mah AT, Van Landeghem L, Gavin HE, Magness ST, Lund PK. 2014. Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1. Endocrinology 155:3302–14
    [Google Scholar]
  93. 93.
    DeClercq V, McMurray DN, Chapkin RS. 2015. Obesity promotes colonic stem cell expansion during cancer initiation. Cancer Lett. 369:336–43
    [Google Scholar]
  94. 94.
    Degirolamo C, Modica S, Palasciano G, Moschetta A. 2011. Bile acids and colon cancer: solving the puzzle with nuclear receptors. Trends Mol. Med. 17:564–72
    [Google Scholar]
  95. 95.
    Fu T, Coulter S, Yoshihara E, Oh TG, Fang S et al. 2019. FXR regulates intestinal cancer stem cell proliferation. Cell 176:1098–112.e18
    [Google Scholar]
  96. 96.
    Biton M, Haber AL, Rogel N, Burgin G, Beyaz S et al. 2018. T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell 175:1307–20.e22
    [Google Scholar]
  97. 97.
    Ringel AE, Drijvers JM, Baker GJ, Catozzi A, Garcia-Canaveras JC et al. 2020. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183:1848–66.e26
    [Google Scholar]
  98. 98.
    Yang J, Wei H, Zhou Y, Szeto CH, Li C et al. 2022. High-fat diet promotes colorectal tumorigenesis through modulating gut microbiota and metabolites. Gastroenterology 162:135–49.e2
    [Google Scholar]
  99. 99.
    Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S et al. 2014. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature 514:508–12
    [Google Scholar]
  100. 100.
    Liu YS, Wu QJ, Lv JL, Jiang YT, Sun H et al. 2021. Dietary carbohydrate and diverse health outcomes: umbrella review of 30 systematic reviews and meta-analyses of 281 observational studies. Front. Nutr. 8:670411
    [Google Scholar]
  101. 101.
    Aliluev A, Tritschler S, Sterr M, Oppenlander L, Hinterdobler J et al. 2021. Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice. Nat. Metab. 3:1202–16
    [Google Scholar]
  102. 102.
    Payne NE, Cross JH, Sander JW, Sisodiya SM. 2011. The ketogenic and related diets in adolescents and adults—a review. Epilepsia 52:1941–48
    [Google Scholar]
  103. 103.
    Li J, Zhang H, Dai Z. 2021. Cancer treatment with the ketogenic diet: a systematic review and meta-analysis of animal studies. Front. Nutr. 8:594408
    [Google Scholar]
  104. 104.
    Cheng CW, Biton M, Haber AL, Gunduz N, Eng G et al. 2019. Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet. Cell 178:1115–31.e15
    [Google Scholar]
  105. 105.
    Dmitrieva-Posocco O, Wong AC, Lundgren P, Golos AM, Descamps HC et al. 2022. β-Hydroxybutyrate suppresses colorectal cancer. Nature 605:160–65
    [Google Scholar]
  106. 106.
    Bruno DS, Berger NA. 2020. Impact of bariatric surgery on cancer risk reduction. Ann. Transl. Med. 8:S13
    [Google Scholar]
  107. 107.
    Mackenzie H, Markar SR, Askari A, Faiz O, Hull M et al. 2018. Obesity surgery and risk of cancer. Br. J. Surg. 105:1650–57
    [Google Scholar]
  108. 108.
    Schauer DP, Feigelson HS, Koebnick C, Caan B, Weinmann S et al. 2019. Bariatric surgery and the risk of cancer in a large multisite cohort. Ann. Surg. 269:95–101
    [Google Scholar]
  109. 109.
    Bailly L, Fabre R, Pradier C, Iannelli A. 2020. Colorectal cancer risk following bariatric surgery in a nationwide study of French individuals with obesity. JAMA Surg. 155:395–402
    [Google Scholar]
  110. 110.
    Almazeedi S, El-Abd R, Al-Khamis A, Albatineh AN, Al-Sabah S 2020. Role of bariatric surgery in reducing the risk of colorectal cancer: a meta-analysis. Br. J. Surg. 107:348–54
    [Google Scholar]
  111. 111.
    Kedrin D, Gandhi SC, Wolf M, Roper J, Yilmaz O et al. 2017. Bariatric surgery prior to index screening colonoscopy is associated with a decreased rate of colorectal adenomas in obese individuals. Clin. Transl. Gastroenterol. 8:e73
    [Google Scholar]
  112. 112.
    Satoh K, Yachida S, Sugimoto M, Oshima M, Nakagawa T et al. 2017. Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. PNAS 114:E7697–706
    [Google Scholar]
  113. 113.
    Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W et al. 2013. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev. Cell 25:463–77
    [Google Scholar]
  114. 114.
    Cheung EC, Lee P, Ceteci F, Nixon C, Blyth K et al. 2016. Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine. Genes Dev. 30:52–63
    [Google Scholar]
  115. 115.
    Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM et al. 2019. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 47:D941–47
    [Google Scholar]
  116. 116.
    Nie X, Liu H, Liu L, Wang YD, Chen WD. 2020. Emerging roles of Wnt ligands in human colorectal cancer. Front. Oncol. 10:1341
    [Google Scholar]
  117. 117.
    Kimmelman AC. 2015. Metabolic dependencies in RAS-driven cancers. Clin. Cancer Res. 21:1828–34
    [Google Scholar]
  118. 118.
    Labuschagne CF, Zani F, Vousden KH. 2018. Control of metabolism by p53—cancer and beyond. Biochim. Biophys. Acta Rev. Cancer 1870:32–42
    [Google Scholar]
  119. 119.
    Pate KT, Stringari C, Sprowl-Tanio S, Wang K, TeSlaa T et al. 2014. Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J. 33:1454–73
    [Google Scholar]
  120. 120.
    Worby CA, Dixon JE. 2014. PTEN. Annu. Rev. Biochem. 83:641–69
    [Google Scholar]
  121. 121.
    Mukhopadhyay S, Vander Heiden MG, McCormick F. 2021. The metabolic landscape of RAS-driven cancers from biology to therapy. Nat. Cancer 2:271–83
    [Google Scholar]
  122. 122.
    Smith AL, Whitehall JC, Bradshaw C, Gay D, Robertson F et al. 2020. Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis. Nat. Cancer 1:976–89
    [Google Scholar]
  123. 123.
    Ohshima K, Nojima S, Tahara S, Kurashige M, Kawasaki K et al. 2020. Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine. Nat. Metab 2:81–96
    [Google Scholar]
  124. 124.
    Bensard CL, Wisidagama DR, Olson KA, Berg JA, Krah NM et al. 2020. Regulation of tumor initiation by the mitochondrial pyruvate carrier. Cell Metab. 31:284–300.e7
    [Google Scholar]
  125. 125.
    Ma L, Tao Y, Duran A, Llado V, Galvez A et al. 2013. Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis. Cell 152:599–611
    [Google Scholar]
  126. 126.
    Phillips CM, Zatarain JR, Nicholls ME, Porter C, Widen SG et al. 2017. Upregulation of cystathionine-β-synthase in colonic epithelia reprograms metabolism and promotes carcinogenesis. Cancer Res. 77:5741–54
    [Google Scholar]
  127. 127.
    Lambert AW, Weinberg RA. 2021. Linking EMT programmes to normal and neoplastic epithelial stem cells. Nat. Rev. Cancer 21:325–38
    [Google Scholar]
  128. 128.
    Gao W, Chen L, Ma Z, Du Z, Zhao Z et al. 2013. Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology 145:636–46.e5
    [Google Scholar]
  129. 129.
    Wu Z, Wei D, Gao W, Xu Y, Hu Z et al. 2015. TPO-induced metabolic reprogramming drives liver metastasis of colorectal cancer CD110+ tumor-initiating cells. Cell Stem Cell 17:47–59
    [Google Scholar]
  130. 130.
    Bergers G, Fendt SM. 2021. The metabolism of cancer cells during metastasis. Nat. Rev. Cancer 21:162–80
    [Google Scholar]
  131. 131.
    Wang D, Fu L, Wei J, Xiong Y, DuBois RN. 2019. PPARδ mediates the effect of dietary fat in promoting colorectal cancer metastasis. Cancer Res. 79:4480–90
    [Google Scholar]
  132. 132.
    Wang YN, Zeng ZL, Lu J, Wang Y, Liu ZX et al. 2018. CPT1A-mediated fatty acid oxidation promotes colorectal cancer cell metastasis by inhibiting anoikis. Oncogene 37:6025–40
    [Google Scholar]
  133. 133.
    Xiang L, Mou J, Shao B, Wei Y, Liang H et al. 2019. Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization. Cell Death Dis. 10:40
    [Google Scholar]
  134. 134.
    Xiang L, Xie G, Liu C, Zhou J, Chen J et al. 2013. Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation. Biochim. Biophys. Acta Mol. Cell Res. 1833:2996–3005
    [Google Scholar]
  135. 135.
    Lu H, Samanta D, Xiang L, Zhang H, Hu H et al. 2015. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. PNAS 112:E4600–9
    [Google Scholar]
  136. 136.
    Nguyen A, Loo JM, Mital R, Weinberg EM, Man FY et al. 2016. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis. J. Clin. Investig. 126:681–94
    [Google Scholar]
  137. 137.
    Cen B, Lang JD, Du Y, Wei J, Xiong Y et al. 2020. Prostaglandin E2 induces miR675-5p to promote colorectal tumor metastasis via modulation of p53 expression. Gastroenterology 158:971–84.e10
    [Google Scholar]
  138. 138.
    Wang D, Fu L, Sun H, Guo L, DuBois RN. 2015. Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice. Gastroenterology 149:1884–95.e4
    [Google Scholar]
  139. 139.
    Loo JM, Scherl A, Nguyen A, Man FY, Weinberg E et al. 2015. Extracellular metabolic energetics can promote cancer progression. Cell 160:393–406
    [Google Scholar]
  140. 140.
    Kurth I, Yamaguchi N, Andreu-Agullo C, Tian HS, Sridhar S et al. 2021. Therapeutic targeting of SLC6A8 creatine transporter suppresses colon cancer progression and modulates human creatine levels. Sci. Adv. 7:eabi7511
    [Google Scholar]
  141. 141.
    Yamaguchi N, Weinberg EM, Nguyen A, Liberti MV, Goodarzi H et al. 2019. PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis. eLife 8:e52135
    [Google Scholar]
  142. 142.
    Donaldson GP, Lee SM, Mazmanian SK. 2016. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14:20–32
    [Google Scholar]
  143. 143.
    Song M, Chan AT, Sun J. 2020. Influence of the gut microbiome, diet, and environment on risk of colorectal cancer. Gastroenterology 158:322–40
    [Google Scholar]
  144. 144.
    Lee YS, Kim TY, Kim Y, Lee SH, Kim S et al. 2018. Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host Microbe 24:833–46.e6
    [Google Scholar]
  145. 145.
    Pleguezuelos-Manzano C, Puschhof J, Clevers H. 2022. Gut microbiota in colorectal cancer: associations, mechanisms, and clinical approaches. Annu. Rev. Cancer Biol. 6:65–84
    [Google Scholar]
  146. 146.
    Han H, Safe S, Jayaraman A, Chapkin RS. 2021. Diet-host-microbiota interactions shape aryl hydrocarbon receptor ligand production to modulate intestinal homeostasis. Annu. Rev. Nutr. 41:455–78
    [Google Scholar]
  147. 147.
    Buc E, Dubois D, Sauvanet P, Raisch J, Delmas J et al. 2013. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLOS ONE 8:e56964
    [Google Scholar]
  148. 148.
    Wilson MR, Jiang Y, Villalta PW, Stornetta A, Boudreau PD et al. 2019. The human gut bacterial genotoxin colibactin alkylates DNA. Science 363:eaar7785
    [Google Scholar]
  149. 149.
    Zhan Y, Chen PJ, Sadler WD, Wang F, Poe S et al. 2013. Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury. Cancer Res. 73:7199–210
    [Google Scholar]
  150. 150.
    Bell HN, Rebernick RJ, Goyert J, Singhal R, Kuljanin M et al. 2022. Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance. Cancer Cell 40:185–200.e6
    [Google Scholar]
  151. 151.
    Biller LH, Schrag D. 2021. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA 325:669–85
    [Google Scholar]
  152. 152.
    Longley DB, Harkin DP, Johnston PG. 2003. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3:330–38
    [Google Scholar]
  153. 153.
    Tegnebratt T, Lu L, Lee L, Meresse V, Tessier J et al. 2013. [18 F]FDG-PET imaging is an early non-invasive pharmacodynamic biomarker for a first-in-class dual MEK/Raf inhibitor, RO5126766 (CH5126766), in preclinical xenograft models. EJNMMI Res 3:67
    [Google Scholar]
  154. 154.
    Toda K, Kawada K, Iwamoto M, Inamoto S, Sasazuki T et al. 2016. Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia 18:654–65
    [Google Scholar]
  155. 155.
    Carr RM, Qiao G, Qin J, Jayaraman S, Prabhakar BS, Maker AV. 2016. Targeting the metabolic pathway of human colon cancer overcomes resistance to TRAIL-induced apoptosis. Cell Death Discov. 2:16067
    [Google Scholar]
  156. 156.
    Zhang ZJ, Zheng ZJ, Kan H, Song Y, Cui W et al. 2011. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care 34:2323–28
    [Google Scholar]
  157. 157.
    Tomimoto A, Endo H, Sugiyama M, Fujisawa T, Hosono K et al. 2008. Metformin suppresses intestinal polyp growth in ApcMin/+ mice. Cancer Sci. 99:2136–41
    [Google Scholar]
  158. 158.
    Hosono K, Endo H, Takahashi H, Sugiyama M, Uchiyama T et al. 2010. Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinase. Mol. Carcinog. 49:662–71
    [Google Scholar]
  159. 159.
    Jia Y, Ma Z, Liu X, Zhou W, He S et al. 2015. Metformin prevents DMH-induced colorectal cancer in diabetic rats by reversing the Warburg effect. Cancer Med. 4:1730–41
    [Google Scholar]
  160. 160.
    Janzer A, German NJ, Gonzalez-Herrera KN, Asara JM, Haigis MC, Struhl K. 2014. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells. PNAS 111:10574–79
    [Google Scholar]
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