Autophagy is required for PDAC glutamine metabolism

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Seo, Ju Won ^a   Choi, Jungwon ^b   Lee, So Yeon ^a   Sung, Suhyun ^b   Yoo, Hyun Ju ^c   Kang, Min Ji ^a   Cheong, Heesun ^b   Son, Jaekyoung ^a  

^a University of Ulsan College of Medicine   (South Korea)

^b National Cancer Center   (South Korea)

^c Asan Medical Center   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; GLUCOSE; GLUTAMINE; MUTANT PROTEIN; RAS PROTEIN; TFEB PROTEIN, HUMAN;

ANIMAL; APOPTOSIS; AUTOPHAGY; BAGG ALBINO MOUSE; BIOLOGICAL MODEL; CELL SURVIVAL; CITRIC ACID CYCLE; DEFICIENCY; FEMALE; GENETICS; HUMAN; INTRACELLULAR SPACE; METABOLISM; NUDE MOUSE; PANCREAS CARCINOMA; PINOCYTOSIS; TRANSPORT AT THE CELLULAR LEVEL; TUMOR CELL LINE;

ANIMALS; APOPTOSIS; AUTOPHAGY; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; BIOLOGICAL TRANSPORT; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CELL SURVIVAL; CITRIC ACID CYCLE; FEMALE; GLUCOSE; GLUTAMINE; HUMANS; INTRACELLULAR SPACE; MICE, INBRED BALB C; MICE, NUDE; MODELS, BIOLOGICAL; MUTANT PROTEINS; PINOCYTOSIS; RAS PROTEINS;

EID: 84999273647     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep37594     Document Type: Article

References (44)

1. Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. & Depinho, R. A. Genetics and biology of pancreatic ductal adenocarcinoma. Genes & development 20, 1218-1249, doi: 10.1101/gad.1415606 (2006).
2. Ben-Josef, E. & Lawrence, T. S. Chemoradiotherapy for unresectable pancreatic cancer. International journal of clinical oncology 13, 121-126, doi: 10.1007/s10147-007-0763-x (2008).
3. Hidalgo, M. Pancreatic cancer. The New England journal of medicine 362, 1605-1617, doi: 10.1056/NEJMra0901557 (2010).
4. Ward, P. S. & Thompson, C. B. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer cell 21, 297-308, doi: 10.1016/j.ccr.2012.02.014 (2012).
5. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033, doi: 10.1126/science.1160809 (2009).
6. Wise, D. R. & Thompson, C. B. Glutamine addiction: a new therapeutic target in cancer. Trends in biochemical sciences 35, 427-433, doi: 10.1016/j.tibs.2010.05.003 (2010).
7. Son, J. et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496, 101-105, doi: 10.1038/nature12040 (2013).
8. Chakrabarti, G. et al. Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ss-lapachone. Cancer & metabolism 3, 12, doi: 10.1186/s40170-015-0137-1 (2015).
9. Bar-Sagi, D. & Feramisco, J. R. Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. Science 233, 1061-1068 (1986).
10. Porat-Shliom, N., Kloog, Y. & Donaldson, J. G. A unique platform for H-Ras signaling involving clathrin-independent endocytosis. Molecular biology of the cell 19, 765-775, doi: 10.1091/mbc.E07-08-0841 (2008).
11. Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633-637, doi: 10.1038/nature12138 (2013).
12. Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075, doi: 10.1038/nature06639 (2008).
13. Rabinowitz, J. D. & White, E. Autophagy and metabolism. Science 330, 1344-1348, doi: 10.1126/science.1193497 (2010).
14. Egan, D. F. et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331, 456-461, doi: 10.1126/science.1196371 (2011).
15. Kim, J., Kundu, M., Viollet, B. & Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology 13, 132-141, doi: 10.1038/ncb2152 (2011).
16. Hardie, D. G., Ross, F. A. & Hawley, S. A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nature reviews. Molecular cell biology 13, 251-262, doi: 10.1038/nrm3311 (2012).
17. Ye, J. et al. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. The EMBO journal 29, 2082-2096, doi: 10.1038/emboj.2010.81 (2010).
18. Marino, G. et al. Regulation of autophagy by cytosolic acetyl-coenzyme A. Molecular cell 53, 710-725, doi: 10.1016/j. molcel.2014.01.016 (2014).
19. Yang, S. et al. Pancreatic cancers require autophagy for tumor growth. Genes & development 25, 717-729, doi: 10.1101/gad.2016111 (2011).
20. Guo, J. Y. et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes & development 25, 460-470, doi: 10.1101/gad.2016311 (2011).
21. Bjorkoy, G. et al. Monitoring autophagic degradation of p62/SQSTM1. Methods in enzymology 452, 181-197, doi: 10.1016/S0076- 6879(08)03612-4 (2009).
22. Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 151-175 (2008).
23. Hensley, C. T., Wasti, A. T. & DeBerardinis, R. J. Glutamine and cancer: cell biology, physiology, and clinical opportunities. The Journal of clinical investigation 123, 3678-3684, doi: 10.1172/JCI69600 (2013).
24. Fan, J. et al. Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Molecular systems biology 9, 712, doi: 10.1038/msb.2013.65 (2013).
25. DeBerardinis, R. J. et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences of the United States of America 104, 19345-19350, doi: 10.1073/pnas.0709747104 (2007).
26. DeBerardinis, R. J. & Cheng, T. Qs next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29, 313-324, doi: 10.1038/onc.2009.358 (2010).
27. Ying, H. et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149, 656-670, doi: 10.1016/j.cell.2012.01.058 (2012).
28. Settembre, C. et al. TFEB links autophagy to lysosomal biogenesis. Science 332, 1429-1433, doi: 10.1126/science.1204592 (2011).
29. Sung, S., Choi, J. & Cheong, H. Catabolic pathways regulated by mTORC1 are pivotal for survival and growth of cancer cells expressing mutant Ras. Oncotarget 6, 40405-40417, doi: 10.18632/oncotarget.6334 (2015).
30. Kamphorst, J. J. et al. Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer research 75, 544-553, doi: 10.1158/0008-5472.CAN-14-2211 (2015).
31. Ivanov, A. I. Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods in molecular biology 440, 15-33, doi: 10.1007/978-1-59745-178-9-2 (2008).
32. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762-765, doi: 10.1038/nature07823 (2009).
33. Wise, D. R. et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proceedings of the National Academy of Sciences of the United States of America 105, 18782-18787, doi: 10.1073/ pnas.0810199105 (2008).
34. Raben, N. & Puertollano, R. TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress. Annu Rev Cell Dev Biol, doi: 10.1146/annurev-cellbio-111315-125407 (2016).
35. Settembre, C. & Ballabio, A. TFEB regulates autophagy: an integrated coordination of cellular degradation and recycling processes. Autophagy 7, 1379-1381, doi: 10.4161/auto.7.11.17166 (2011).
36. Settembre, C. et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nature cell biology 15, 647-658, doi: 10.1038/ncb2718 (2013).
37. Nicklin, P. et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521-534, doi: 10.1016/j. cell.2008.11.044 (2009).
38. Martina, J. A., Chen, Y., Gucek, M. & Puertollano, R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8, 903-914, doi: 10.4161/auto.19653 (2012).
39. Strohecker, A. M. et al. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer discovery 3, 1272-1285, doi: 10.1158/2159-8290.CD-13-0397 (2013).
40. Zhu, Y. et al. L-Glutamine deprivation induces autophagy and alters the mTOR and MAPK signaling pathways in porcine intestinal epithelial cells. Amino acids 47, 2185-2197, doi: 10.1007/s00726-014-1785-0 (2015).
41. Gaglio, D., Soldati, C., Vanoni, M., Alberghina, L. & Chiaradonna, F. Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts. PloS one 4, e4715, doi: 10.1371/journal.pone.0004715 (2009).
42. Wu, M. C., Arimura, G. K. & Yunis, A. A. Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase. International journal of cancer. Journal international du cancer 22, 728-733 (1978).
43. Guo, J. Y. et al. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells. Genes & development 30, 1704-1717, doi: 10.1101/gad.283416.116 (2016).
44. Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032-1036, doi: 10.1038/nature03029 (2004).