Display options
Cite
Snyder V, Reed-Newman TC, Arnold L, et al. Cancer Stem Cell Metabolism and Potential Therapeutic Targets. Front Oncol. 2018;8:203doi: 10.3389/fonc.2018.00203.
Snyder, V., Reed-Newman, T. C., Arnold, L., Thomas, S. M., & Anant, S. (2018). Cancer Stem Cell Metabolism and Potential Therapeutic Targets. Frontiers in oncology, 8203. https://doi.org/10.3389/fonc.2018.00203
Snyder, Vusala, et al. "Cancer Stem Cell Metabolism and Potential Therapeutic Targets." Frontiers in oncology vol. 8 (2018): 203. doi: https://doi.org/10.3389/fonc.2018.00203
Snyder V, Reed-Newman TC, Arnold L, Thomas SM, Anant S. Cancer Stem Cell Metabolism and Potential Therapeutic Targets. Front Oncol. 2018 Jun 05;8:203. doi: 10.3389/fonc.2018.00203. eCollection 2018. PMID: 29922594; PMCID: PMC5996058.
Copy Download .nbib Format: NLM
Share it on

Front Oncol. 2018 Jun 05;8:203. doi: 10.3389/fonc.2018.00203. eCollection 2018.

Cancer Stem Cell Metabolism and Potential Therapeutic Targets.

Frontiers in oncology

Vusala Snyder, Tamika C Reed-Newman, Levi Arnold, Sufi Mary Thomas, Shrikant Anant

Affiliations

  1. Department of Otolaryngology, University of Kansas Medical Center, Kansas City, KS, United States.
  2. Department of General Surgery, University of Kansas Medical Center, Kansas City, KS, United States.
  3. Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United States.
  4. Cancer Biology, University of Kansas Medical Center, Kansas City, KS, United States.

PMID: 29922594 PMCID: PMC5996058 DOI: 10.3389/fonc.2018.00203

Abstract

Malignant tumors contain heterogeneous populations of cells in various states of proliferation and differentiation. The presence of cancer stem or initiating cells is a well-established concept wherein quiescent and poorly differentiated cells within a tumor mass contribute to drug resistance, and under permissive conditions, are responsible for tumor recurrence and metastasis. A number of studies have identified molecular markers that are characteristic of tissue-specific cancer stem cells (CSCs). Isolation of CSCs has enabled studies on the metabolic status of CSCs. As metabolic plasticity is a hallmark of cancer cell adaptation, the intricacies of CSC metabolism and their phenotypic behavior are critical areas of research. Unlike normal stem cells, which rely heavily on oxidative phosphorylation (OXPHOS) as their primary source of energy, or cancer cells, which are primarily glycolytic, CSCs demonstrate a unique metabolic flexibility. CSCs can switch between OXPHOS and glycolysis in the presence of oxygen to maintain homeostasis and, thereby, promote tumor growth. Here, we review key factors that impact CSC metabolic phenotype including heterogeneity of CSCs across different histologic tumor types, tissue-specific variations, tumor microenvironment, and CSC niche. Furthermore, we discuss how targeting key players of glycolytic and mitochondrial pathways has shown promising results in cancer eradication and attenuation of disease recurrence in preclinical models. In addition, we highlight studies on other potential therapeutic targets including complex interactions within the microenvironment and cellular communications in the CSC niche to interfere with CSC growth, resistance, and metastasis.

Keywords: cancer stem cell markers; metabolism; microenvironment; stem cells; targets

References

  1. Oncotarget. 2014 Nov 30;5(22):11029-37 - PubMed
  2. Science. 1956 Feb 24;123(3191):309-14 - PubMed
  3. Br J Cancer. 2010 Aug 10;103(4):439-45 - PubMed
  4. Clin Cancer Res. 2005 Feb 1;11(3):1154-9 - PubMed
  5. World J Biol Chem. 2015 Aug 26;6(3):148-61 - PubMed
  6. Nat Med. 2004 Aug;10(8):858-64 - PubMed
  7. Oncotarget. 2016 Jan 19;7(3):2910-20 - PubMed
  8. Cell Metab. 2011 Aug 3;14(2):264-71 - PubMed
  9. Mol Cancer Ther. 2011 Dec;10(12):2350-62 - PubMed
  10. Cell Metab. 2015 Oct 6;22(4):590-605 - PubMed
  11. Oncogene. 2018 Feb 22;37(8):1119 - PubMed
  12. Cell Stem Cell. 2012 Nov 2;11(5):596-606 - PubMed
  13. Cancer Metastasis Rev. 2009 Dec;28(3-4):291-304 - PubMed
  14. Breast Cancer Res. 2010;12(6):R94 - PubMed
  15. EMBO Rep. 2010 Oct;11(10):805-10 - PubMed
  16. Mol Cancer Ther. 2011 Nov;10(11):2146-56 - PubMed
  17. Cell Stem Cell. 2010 May 7;6(5):421-32 - PubMed
  18. J Clin Invest. 2005 Jun;115(6):1503-21 - PubMed
  19. FASEB J. 2004 Aug;18(11):1303-5 - PubMed
  20. Cancer Lett. 2007 Dec 18;258(2):286-90 - PubMed
  21. MAbs. 2009 Jan-Feb;1(1):12-25 - PubMed
  22. Pharmacol Ther. 2015 Nov;155:1-10 - PubMed
  23. Cancer Cell. 2013 Jun 10;23 (6):811-25 - PubMed
  24. Am J Physiol Cell Physiol. 2007 Jan;292(1):C125-36 - PubMed
  25. Genes Dev. 2012 Sep 1;26(17):1926-44 - PubMed
  26. Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):554-63 - PubMed
  27. Nature. 2017 Mar 16;543(7645):424-427 - PubMed
  28. BMC Cancer. 2013 Feb 19;13:81 - PubMed
  29. FASEB J. 2007 Dec;21(14):3777-85 - PubMed
  30. Oncotarget. 2015 Dec 15;6(40):42651-60 - PubMed
  31. J Biol Chem. 2008 May 23;283(21):14581-9 - PubMed
  32. Prog Lipid Res. 2013 Apr;52(2):220-30 - PubMed
  33. Bioessays. 2009 Oct;31(10):1038-49 - PubMed
  34. Nature. 2009 Sep 3;461(7260):109-13 - PubMed
  35. PLoS One. 2015 Nov 03;10(11):e0141919 - PubMed
  36. Stem Cells. 2014 Nov;32(11):2845-57 - PubMed
  37. J Clin Invest. 2011 Oct;121(10):3804-9 - PubMed
  38. Biomed Opt Express. 2012 Jan 1;3(1):75-85 - PubMed
  39. Springerplus. 2013 Jul 04;2(1):301 - PubMed
  40. Chin J Cancer. 2011 Aug;30(8):508-25 - PubMed
  41. Breast Cancer Res Treat. 2014 Aug;146(3):525-34 - PubMed
  42. Exp Mol Med. 2013 Oct 04;45:e45 - PubMed
  43. Cell Stem Cell. 2014 Mar 6;14(3):275-91 - PubMed
  44. Science. 2006 Mar 31;311(5769):1880-5 - PubMed
  45. Cancer Cell. 2013 Mar 18;23 (3):316-31 - PubMed
  46. Genet Mol Res. 2014 Apr 14;13(2):2796-805 - PubMed
  47. Cell Metab. 2016 Jan 12;23 (1):206-19 - PubMed
  48. Curr Opin Clin Nutr Metab Care. 2010 Jul;13(4):466-70 - PubMed
  49. Conf Proc IEEE Eng Med Biol Soc. 2014;2014:4759-62 - PubMed
  50. Nat Rev Cancer. 2014 Sep;14(9):611-22 - PubMed
  51. J Cell Biochem. 2014 Feb;115(2):368-79 - PubMed
  52. J Drug Target. 2015;23(7-8):605-18 - PubMed
  53. PLoS One. 2014 Jan 07;9(1):e84941 - PubMed
  54. Biol Direct. 2016 Aug 23;11:40 - PubMed
  55. Oncol Rep. 2012 Aug;28(2):465-72 - PubMed
  56. Exp Hematol Oncol. 2013 Jul 01;2(1):17 - PubMed
  57. Prostate Cancer Prostatic Dis. 2015 Dec;18(4):303-9 - PubMed
  58. IUBMB Life. 2015 Sep;67(9):687-93 - PubMed
  59. Curr Stem Cell Res Ther. 2012 May;7(3):197-216 - PubMed
  60. Exp Cell Res. 2014 Oct 15;328(1):44-57 - PubMed
  61. Cell Stem Cell. 2010 Aug 6;7(2):150-61 - PubMed
  62. Evid Based Complement Alternat Med. 2013;2013:590393 - PubMed
  63. Neurosurgery. 2011 Feb;68(2):531-45; discussion 545 - PubMed
  64. Cell Metab. 2016 Mar 8;23 (3):517-28 - PubMed
  65. Carcinogenesis. 2017 Feb 1;38(2):119-133 - PubMed
  66. J Mol Med (Berl). 2011 Feb;89(2):95-107 - PubMed
  67. Mol Cancer. 2017 Jan 30;16(1):10 - PubMed
  68. Life Sci. 2010 Apr 24;86(17-18):631-7 - PubMed
  69. J Biol Chem. 2011 Sep 16;286(37):32843-53 - PubMed
  70. Oral Oncol. 2014 Jul;50(7):633-9 - PubMed
  71. Haematologica. 2009 Nov;94(11):1590-4 - PubMed
  72. Cancer Lett. 2010 Feb 1;288(1):1-9 - PubMed
  73. Nat Med. 2012 Sep;18(9):1350-8 - PubMed
  74. Oncotarget. 2015 Jun 20;6(17 ):14777-95 - PubMed
  75. J Pathol. 2013 Feb;229(3):355-78 - PubMed
  76. J Clin Invest. 2010 Jan;120(1):142-56 - PubMed
  77. Stem Cells. 2014 Jul;32(7):1734-45 - PubMed
  78. Nature. 2011 Nov 20;481(7381):385-8 - PubMed
  79. Cell Cycle. 2014;13(7):1152-61 - PubMed
  80. Cancer Res. 2006 May 1;66(9):4553-7 - PubMed
  81. Oncogene. 2011 Dec 15;30(50):4930-40 - PubMed
  82. Cell. 2007 May 4;129(3):465-72 - PubMed
  83. Curr Cancer Drug Targets. 2011 Jun;11(5):572-85 - PubMed
  84. PLoS One. 2014 Sep 05;9(9):e107013 - PubMed
  85. Clin Cancer Res. 2010 Jun 15;16(12):3121-9 - PubMed
  86. Biochem Biophys Res Commun. 2014 Nov 14;454(2):335-40 - PubMed
  87. Nature. 2001 Nov 1;414(6859):105-11 - PubMed
  88. Br J Cancer. 2016 Jun 14;114(12 ):1305-12 - PubMed
  89. PLoS One. 2011;6(11):e28068 - PubMed
  90. Cancer Gene Ther. 2011 Dec;18(12):897-905 - PubMed
  91. Trends Immunol. 2015 Feb;36(2):92-101 - PubMed
  92. Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G449-68 - PubMed
  93. Oncotarget. 2014 Jun 30;5(12):3970-82 - PubMed
  94. Tumour Biol. 2015 Apr;36(4):3119-26 - PubMed
  95. Int J Immunother Cancer Res. 2016;2(1):14-16 - PubMed
  96. Cell Metab. 2015 Oct 6;22(4):577-89 - PubMed
  97. Science. 2009 May 22;324(5930):1029-33 - PubMed
  98. Cancer Res. 2007 Feb 15;67(4):1472-86 - PubMed
  99. Clin Pharmacol Ther. 2011 Apr;89(4):491-502 - PubMed
  100. Int J Cancer. 2011 Aug 15;129(4):820-31 - PubMed
  101. Cell Cycle. 2015;14(1):86-98 - PubMed
  102. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16062-7 - PubMed
  103. Cytotechnology. 2013 Aug;65(4):505-12 - PubMed
  104. Oncotarget. 2014 Jun 30;5(12):4305-19 - PubMed
  105. Breast Cancer Res. 2016 May 24;18(1):55 - PubMed
  106. BMC Cancer. 2008 May 14;8:135 - PubMed
  107. Nature. 2009 Apr 9;458(7239):780-3 - PubMed
  108. Stem Cells. 2016 May;34(5):1163-76 - PubMed
  109. Korean J Pathol. 2013 Apr;47(2):116-23 - PubMed
  110. Cell Death Differ. 2014 Jan;21(1):124-35 - PubMed
  111. Cell Rep. 2015 Mar 3;10 (8):1335-48 - PubMed
  112. Cell Death Dis. 2014 Jul 17;5:e1336 - PubMed
  113. Oncotarget. 2015 Mar 10;6(7):4569-84 - PubMed
  114. BMB Rep. 2017 Jun;50(6):285-298 - PubMed
  115. Cancer Sci. 2014 Nov;105(11):1411-20 - PubMed
  116. Cancer Res. 2008 Sep 1;68(17):6932-41 - PubMed
  117. Oncotarget. 2016 Mar 8;7(10 ):11018-32 - PubMed
  118. Cancer Treat Rev. 2015 Jul;41(7):623-33 - PubMed
  119. Cell Cycle. 2010 Sep 15;9(18):3807-14 - PubMed
  120. Stem Cells Transl Med. 2015 Sep;4(9):1033-43 - PubMed
  121. Cancer Res. 2005 Jan 1;65(1):177-85 - PubMed
  122. Oncotarget. 2015 Oct 13;6(31):30453-71 - PubMed
  123. Oncotarget. 2015 Oct 13;6(31):30472-86 - PubMed
  124. J Proteomics. 2013 Oct 8;91:84-96 - PubMed
  125. Cell Stem Cell. 2013 Mar 7;12(3):329-41 - PubMed
  126. Cancer Res. 2012 Mar 15;72(6):1438-48 - PubMed
  127. Cell Cycle. 2010 Sep 1;9(17):3506-14 - PubMed
  128. Int J Mol Sci. 2014 Dec 26;16(1):439-51 - PubMed
  129. Stem Cells. 2010 Apr;28(4):721-33 - PubMed
  130. Expert Opin Ther Targets. 2013 Jun;17(6):681-93 - PubMed

Publication Types

Grant support