Skip to main content
SpringerLink
Log in
Book cover

Targeting Autophagy in Cancer Therapy pp 99–116Cite as

Adult and Cancer Stem Cells: Perspectives on Autophagic Fate Determinations and Molecular Intervention

  • Chapter
  • First Online:

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Autophagy is a highly conserved mechanism for the maintenance of cellular homeostasis and functionality in pluripotent stem cells, adult stem cells, and normal somatic cells. Cytoprotective roles of autophagy are essential for eliminating damaged subcellular organelles like mitochondria and protein aggregates, thereby reducing reactive oxygen species (ROS) levels and promoting normal or cancer cell survival. We clarify multiple autophagic inducers, default pathway sensors, and regulators in various stages of stem cells. Of note, with autophagy deficiency, there are two major autophagy-associated outcomes, including pro-autophagic cell survival and death. Clearly, the fates of autophagic determination are tightly regulated by their microenvironments, cell types, and the interplay among multiple cell death machineries related to autophagy, apoptosis, and necrosis. Based on the above fundamental autophagic differences among various cell types, we propose a new concept, balanced autophagy, which sheds light on an equilibrium state between pro-autophagic cell survival and death. We further suggest new strategies targeting therapeutic-resistant cancer stem cells that emphasize the modulatory effects of pro-autophagic cell death in intractable cancer cells.

The original version of this chapter was revised. An erratum to this chapter can be found at DOI http://dx.doi.org/10.1007/978-3-319-42740-9_8

An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-3-319-42740-9_8

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alers, S., Loffler, A. S., & Wesselborg, S. (2012). Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks. Molecular and Cellular Biology, 32(1), 2–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianco, P., & Robey, P. G. (2015). Skeletal stem cells. Development, 142(6), 1023–1027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchser, W. J., Laskow, T. C., Pavlik, P. J., et al. (2012). Cell-mediated autophagy promotes cancer cell survival. Cancer Research, 72(12), 2970–2979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canto, C., Jiang, L. Q., Deshmukh, A. S., et al. (2010). Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metabolism, 11(3), 213–219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaachouay, H., Fehrenbacher, B., Toulany, M., et al. (2015). AMPK-independent autophagy promotes radioresistance of human tumor cells under clinical relevant hypoxia in vitro. Radiotherapy and Oncology, 116(3), 409–416.

    Article  CAS  PubMed  Google Scholar 

  • Chen, H., & Chan, D. C. (2009). Mitochondrial dynamics─Fusion, fission, movement, and mitophagy─In neurodegenerative diseases. Human Molecular Genetics, 18(R2), R169–R176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, K. G., Leapman, R. D., Zhang, G., et al. (2009). Influence of melanosome dynamics on melanoma drug sensitivity. Journal of the National Cancer Institute, 101(18), 1259–1271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, K. G., Mallon, B. S., Johnson, K. R., et al. (2014a). Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation. Stem Cell Research, 12(3), 610–621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, K. G., Mallon, B. S., McKay, R. D., et al. (2014b). Human pluripotent stem cell culture: Considerations for maintenance, expansion, and therapeutics. Cell Stem Cell, 14(1), 13–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, K. G., & Sikic, B. I. (2012). Molecular pathways: Regulation and therapeutic implications of multidrug resistance. Clinical Cancer Research, 18(7), 1863–1869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng, Y., Ren, X., Hait, W. N., et al. (2013). Therapeutic targeting of autophagy in disease: Biology and pharmacology. Pharmacological Reviews, 65(4), 1162–1197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng, Y., Wang, B., Zhou, H., et al. (2015). Autophagy is required for the maintenance of liver progenitor cell functionality. Cellular Physiology and Biochemistry, 36(3), 1163–1174.

    Article  CAS  PubMed  Google Scholar 

  • Clarke, M. F., Dick, J. E., Dirks, P. B., et al. (2006). Cancer stem cells—Perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Research, 66(19), 9339–9344.

    Article  CAS  PubMed  Google Scholar 

  • Colman, R. J., Anderson, R. M., Johnson, S. C., et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crighton, D., Wilkinson, S., O’Prey, J., et al. (2006). DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell, 126(1), 121–134.

    Article  CAS  PubMed  Google Scholar 

  • Ding, W. X., & Yin, X. M. (2012). Mitophagy: Mechanisms, pathophysiological roles, and analysis. Biological Chemistry, 393(7), 547–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebato, C., Uchida, T., Arakawa, M., et al. (2008). Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metabolism, 8(4), 325–332.

    Article  CAS  PubMed  Google Scholar 

  • Egan, D. F., Shackelford, D. B., Mihaylova, M. M., et al. (2011). Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science, 331(6016), 456–461.

    Article  CAS  PubMed  Google Scholar 

  • Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    Article  CAS  PubMed  Google Scholar 

  • Feng, Z., Hu, W., de Stanchina, E., et al. (2007). The regulation of AMPK beta1, TSC2, and PTEN expression by p53: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Research, 67(7), 3043–3053.

    Article  CAS  PubMed  Google Scholar 

  • Feng, Z., Zhang, H., Levine, A. J., et al. (2005). The coordinate regulation of the p53 and mTOR pathways in cells. Proceedings of the National Academy of Sciences of the United States of America, 102(23), 8204–8209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleming, A., Noda, T., Yoshimori, T., et al. (2011). Chemical modulators of autophagy as biological probes and potential therapeutics. Nature Chemical Biology, 7(1), 9–17.

    Article  CAS  PubMed  Google Scholar 

  • Gautier, C. A., Kitada, T., & Shen, J. (2008). Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proceedings of the National Academy of Sciences of the United States of America, 105(32), 11364–11369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glinsky, G. V., & Glinsky, V. V. (1996). Apoptosis and metastasis: A superior resistance of metastatic cancer cells to programmed cell death. Cancer Letters, 101(1), 43–51.

    Article  CAS  PubMed  Google Scholar 

  • Gong, C., Bauvy, C., Tonelli, G., et al. (2013). Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Oncogene, 32(18), 2261–2272, 2272e 2261-2211.

    Google Scholar 

  • Gottesman, M. M., Fojo, T., & Bates, S. E. (2002). Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Reviews Cancer, 2(1), 48–58.

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb, E., & Vousden, K. H. (2010). p53 regulation of metabolic pathways. Cold Spring Harbor Perspectives in Biology, 2(4), a001040.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gurumurthy, S., Xie, S. Z., Alagesan, B., et al. (2010). The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature, 468(7324), 659–663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamalainen, R. H., Manninen, T., Koivumaki, H., et al. (2013). Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model. Proceedings of the National Academy of Sciences of the United States of America, 110(38), E3622–E3630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han, J., Hou, W., Goldstein, L. A., et al. (2008). Involvement of protective autophagy in TRAIL resistance of apoptosis-defective tumor cells. Journal of Biological Chemistry, 283(28), 19665–19677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen, M., Chandra, A., Mitic, L. L., et al. (2008). A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genetics, 4(2), e24.

    Article  PubMed  PubMed Central  Google Scholar 

  • He, W., Wang, Q., Xu, J., et al. (2012). Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation. Autophagy, 8(12), 1811–1821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hubbard, V. M., Valdor, R., Patel, B., et al. (2010). Macroautophagy regulates energy metabolism during effector T cell activation. Journal of Immunology, 185(12), 7349–7357.

    Article  CAS  Google Scholar 

  • Ito, K., & Suda, T. (2014). Metabolic requirements for the maintenance of self-renewing stem cells. Nature Reviews Molecular Cell Biology, 15(4), 243–256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, M., Liu, K., Luo, J., et al. (2010). Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. American Journal of Pathology, 176(3), 1181–1192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, P., & Mizushima, N. (2014). Autophagy and human diseases. Cell Research, 24(1), 69–79.

    Article  CAS  PubMed  Google Scholar 

  • Jung, H. S., Chung, K. W., Won Kim, J., et al. (2008). Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metabolism, 8(4), 318–324.

    Article  CAS  PubMed  Google Scholar 

  • Karsli-Uzunbas, G., Guo, J. Y., Price, S., et al. (2014). Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discovery, 4(8), 914–927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenyon, C. J. (2010). The genetics of ageing. Nature, 464(7288), 504–512.

    Article  CAS  PubMed  Google Scholar 

  • Komatsu, M., Kurokawa, H., Waguri, S., et al. (2010). The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nature Cell Biology, 12(3), 213–223.

    CAS  PubMed  Google Scholar 

  • Komatsu, M., Waguri, S., Chiba, T., et al. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, 441(7095), 880–884.

    Article  CAS  PubMed  Google Scholar 

  • Komatsu, M., Waguri, S., Koike, M., et al. (2007). Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell, 131(6), 1149–1163.

    Article  CAS  PubMed  Google Scholar 

  • Kovacs, J. R., Li, C., Yang, Q., et al. (2012). Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery. Cell Death and Differentiation, 19(1), 144–152.

    Article  CAS  PubMed  Google Scholar 

  • Kroemer, G., Marino, G., & Levine, B. (2010). Autophagy and the integrated stress response. Molecular Cell, 40(2), 280–293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubli, D. A., & Gustafsson, A. B. (2012). Mitochondria and mitophagy: The yin and yang of cell death control. Circulation Research, 111(9), 1208–1221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, L., Chen, Y., & Gibson, S. B. (2013). Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cellular Signalling, 25(1), 50–65.

    Article  CAS  PubMed  Google Scholar 

  • Li, J., Hou, N., Faried, A., et al. (2010). Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model. European Journal of Cancer, 46(10), 1900–1909.

    Article  CAS  PubMed  Google Scholar 

  • Liu, D., Yang, Y., Liu, Q., et al. (2011). Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells. Medical Oncology, 28(1), 105–111.

    Article  PubMed  Google Scholar 

  • Lomonaco, S. L., Finniss, S., Xiang, C., et al. (2009). The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells. International Journal of Cancer, 125(3), 717–722.

    Article  CAS  PubMed  Google Scholar 

  • Luciani, F., Spada, M., De Milito, A., et al. (2004). Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. Journal of the National Cancer Institute, 96(22), 1702–1713.

    Article  CAS  PubMed  Google Scholar 

  • Lum, J. J., Bauer, D. E., Kong, M., et al. (2005). Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell, 120(2), 237–248.

    Article  CAS  PubMed  Google Scholar 

  • Marhold, M., Tomasich, E., El-Gazzar, A., et al. (2015). HIF1alpha regulates mTOR signaling and viability of prostate cancer stem cells. Molecular Cancer Research, 13(3), 556–564.

    Article  CAS  PubMed  Google Scholar 

  • Masiero, E., Agatea, L., Mammucari, C., et al. (2009). Autophagy is required to maintain muscle mass. Cell Metabolism, 10(6), 507–515.

    Article  CAS  PubMed  Google Scholar 

  • Matecic, M., Smith, D. L., Pan, X., et al. (2010). A microarray-based genetic screen for yeast chronological aging factors. PLoS Genetics, 6(4), e1000921.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathew, R., Karp, C. M., Beaudoin, B., et al. (2009). Autophagy suppresses tumorigenesis through elimination of p62. Cell, 137(6), 1062–1075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathew, R., Kongara, S., Beaudoin, B., et al. (2007). Autophagy suppresses tumor progression by limiting chromosomal instability. Genes and Development, 21(11), 1367–1381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazure, N. M., & Pouyssegur, J. (2009). Atypical BH3-domains of BNIP3 and BNIP3L lead to autophagy in hypoxia. Autophagy, 5(6), 868–869.

    Article  PubMed  Google Scholar 

  • Meletis, K., Wirta, V., Hede, S. M., et al. (2006). p53 suppresses the self-renewal of adult neural stem cells. Development, 133(2), 363–369.

    Article  CAS  PubMed  Google Scholar 

  • Michaud, M., Martins, I., Sukkurwala, A. Q., et al. (2011). Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science, 334(6062), 1573–1577.

    Article  CAS  PubMed  Google Scholar 

  • Morrison, S. J., & Scadden, D. T. (2014). The bone marrow niche for haematopoietic stem cells. Nature, 505(7483), 327–334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan, H., Cai, N., Li, M., et al. (2013). Autophagic control of cell ‘stemness’. EMBO Molecular Medicine, 5(3), 327–331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papandreou, I., Lim, A. L., Laderoute, K., et al. (2008). Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death and Differentiation, 15(10), 1572–1581.

    Article  CAS  PubMed  Google Scholar 

  • Phadwal, K., Watson, A. S., & Simon, A. K. (2013). Tightrope act: Autophagy in stem cell renewal, differentiation, proliferation, and aging. Cellular and Molecular Life Sciences, 70(1), 89–103.

    Article  CAS  PubMed  Google Scholar 

  • Piskounova, E., Agathocleous, M., Murphy, M. M., et al. (2015). Oxidative stress inhibits distant metastasis by human melanoma cells. Nature, 527(7577), 186–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qu, X., Yu, J., Bhagat, G., Furuya, N., et al. (2003). Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. Journal of Clinical Investigation, 112(12), 1809–1820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravikumar, B., Acevedo-Arozena, A., Imarisio, S., et al. (2005). Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nature Genetics, 37(7), 771–776.

    Article  CAS  PubMed  Google Scholar 

  • Ravikumar, B., Sarkar, S., Davies, J. E., et al. (2010). Regulation of mammalian autophagy in physiology and pathophysiology. Physiological Reviews, 90(4), 1383–1435.

    Article  CAS  PubMed  Google Scholar 

  • Robinton, D. A., & Daley, G. Q. (2012). The promise of induced pluripotent stem cells in research and therapy. Nature, 481(7381), 295–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roesch, A., Fukunaga-Kalabis, M., Schmidt, E. C., et al. (2010). A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell, 141(4), 583–594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rubinsztein, D. C., Marino, G., & Kroemer, G. (2011). Autophagy and aging. Cell, 146(5), 682–695.

    Article  CAS  PubMed  Google Scholar 

  • Rubinsztein, D. C., Ravikumar, B., Acevedo-Arozena, A., et al. (2005). Dyneins, autophagy, aggregation and neurodegeneration. Autophagy, 1(3), 177–178.

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Irastorza, G., Ramos-Casals, M., Brito-Zeron, P., et al. (2010). Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: A systematic review. Annals of the Rheumatic Diseases, 69(1), 20–28.

    Article  CAS  PubMed  Google Scholar 

  • Scherz-Shouval, R., & Elazar, Z. (2011). Regulation of autophagy by ROS: Physiology and pathology. Trends in Biochemical Sciences, 36(1), 30–38.

    Article  CAS  PubMed  Google Scholar 

  • Shacka, J. J., Klocke, B. J., Shibata, M., et al. (2006). Bafilomycin A1 inhibits chloroquine-induced death of cerebellar granule neurons. Molecular Pharmacology, 69(4), 1125–1136.

    Article  CAS  PubMed  Google Scholar 

  • Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., et al. (2003). Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treatment Reviews, 29(4), 297–307.

    Article  CAS  PubMed  Google Scholar 

  • Simonsen, A., Cumming, R. C., Brech, A., et al. (2008). Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy, 4(2), 176–184.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

    Article  CAS  PubMed  Google Scholar 

  • Tan, B. T., Park, C. Y., Ailles, L. E., et al. (2006). The cancer stem cell hypothesis: A work in progress. Laboratory Investigation, 86(12), 1203–1207.

    Article  CAS  PubMed  Google Scholar 

  • Tasdemir, E., Chiara Maiuri, M., Morselli, E., et al. (2008a). A dual role of p53 in the control of autophagy. Autophagy, 4(6), 810–814.

    Article  CAS  PubMed  Google Scholar 

  • Tasdemir, E., Maiuri, M. C., Galluzzi, L., et al. (2008b). Regulation of autophagy by cytoplasmic p53. Nature Cell Biology, 10(6), 676–687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tasdemir, E., Maiuri, M. C., Orhon, I., et al. (2008c). p53 represses autophagy in a cell cycle-dependent fashion. Cell Cycle, 7(19), 3006–3011.

    Article  CAS  PubMed  Google Scholar 

  • Thiery, J. P., Acloque, H., Huang, R. Y., et al. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871–890.

    Article  CAS  PubMed  Google Scholar 

  • Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  • Twig, G., Elorza, A., Molina, A. J., et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO Journal, 27(2), 433–446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vander Heiden, M. G., Locasale, J. W., Swanson, K. D., et al. (2010). Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science, 329(5998), 1492–1499.

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-Martin, A., Cufi, S., Corominas-Faja, B., et al. (2012). Mitochondrial fusion by pharmacological manipulation impedes somatic cell reprogramming to pluripotency: New insight into the role of mitophagy in cell stemness. Aging, 4(6), 393–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagers, A. J., & Weissman, I. L. (2004). Plasticity of adult stem cells. Cell, 116(5), 639–648.

    Article  CAS  PubMed  Google Scholar 

  • Wang, C., Liang, C. C., Bian, Z. C., et al. (2008a). FIP200 is required for maintenance and differentiation of postnatal neural stem cells. Nature Neuroscience, 16(5), 532–542.

    Article  Google Scholar 

  • Wang, S., Xia, P., Ye, B., et al. (2013). Transient activation of autophagy via Sox2-mediated suppression of mTOR is an important early step in reprogramming to pluripotency. Cell Stem Cell, 13(5), 617–625.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Zuo, X., Kucejova, B., et al. (2008b). Reduced cytosolic protein synthesis suppresses mitochondrial degeneration. Nature Cell Biology, 10(9), 1090–1097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warr, M. R., Binnewies, M., Flach, J., Reynaud, D., Garg, T., Malhotra, R., et al. (2013). FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature, 494(7437), 323–327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White, E., Karp, C., Strohecker, A. M., et al. (2010). Role of autophagy in suppression of inflammation and cancer. Current Opinion in Cell Biology, 22(2), 212–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, J. J., Quijano, C., Chen, E., et al. (2009). Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy. Aging, 1(4), 425–437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, S. W., Baek, S. H., Brennan, R. T., et al. (2008). Autophagic death of adult hippocampal neural stem cells following insulin withdrawal. Stem Cells, 26(10), 2602–2610.

    Article  CAS  PubMed  Google Scholar 

  • Yu, J., Parkhitko, A., & Henske, E. P. (2011). Autophagy: An ‘Achilles’ heel of tumorigenesis in TSC and LAM. Autophagy, 7(11), 1400–1401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue, Z., Jin, S., Yang, C., et al. (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15077–15082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, J. (2013). Autophagy and mitophagy in cellular damage control. Redox Biology, 1(1), 19–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, C., & Cuervo, A. M. (2008). Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nature Medicine, 14(9), 959–965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zid, B. M., Rogers, A. N., Katewa, S. D., et al. (2009). 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell, 139(1), 149–160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We would like to thank our colleague Professor R. Padmanabhan for discussion and Ms. Verma Walker, NIH Library Editing Service, for reviewing the manuscript.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, 20057, USA

    Kevin G. Chen & Richard Calderone

  2. NIH Stem Cell Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA

    Kevin G. Chen

Authors
  1. Kevin G. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Calderone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin G. Chen .

Editor information

Editors and Affiliations

  1. Department of Pharmacology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA

    Jin-Ming Yang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Chen, K.G., Calderone, R. (2016). Adult and Cancer Stem Cells: Perspectives on Autophagic Fate Determinations and Molecular Intervention. In: Yang, JM. (eds) Targeting Autophagy in Cancer Therapy. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-319-42740-9_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-42740-9_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-42738-6

  • Online ISBN: 978-3-319-42740-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation