Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism

Nature

Volumn 524, Issue 7565, 2015, Pages 361-365

  Perera, Rushika M ^a,b,c   Stoykova, Svetlana ^a,b   Nicolay, Brandon N ^a,c   Ross, Kenneth N ^a,b,c   Fitamant, Julien ^a,b,c   Boukhali, Myriam ^a   Lengrand, Justine ^a,b   Deshpande, Vikram ^a,c   Selig, Martin K ^a   Ferrone, Cristina R ^a,c   Settleman, Jeff ^a   Stephanopoulos, Gregory ^d   Dyson, Nicholas J ^a,c   Zoncu, Roberto ^e   Ramaswamy, Sridhar ^a,b,c   Haas, Wilhelm ^a,c   Bardeesy, Nabeel ^a,b,c  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d USA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBOHYDRATE; LAMIN; LIPID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; NUCLEOTIDE; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR; BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; MICROPHTHALMIA ASSOCIATED TRANSCRIPTION FACTOR; MITF PROTEIN, HUMAN; TFE3 PROTEIN, HUMAN; TFEB PROTEIN, HUMAN;

AMINO ACID; APOPTOSIS; CANCER; CYTOPLASM; GENE EXPRESSION; GROWTH RATE; HOMEOSTASIS; METABOLISM; PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGY; CANCER CELL CULTURE; CANCER GROWTH; CONTROLLED STUDY; FLUORESCENCE MICROSCOPY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; LYSOSOME; MOUSE; NONHUMAN; NUCLEAR IMPORT; PANCREAS ADENOCARCINOMA; PINOCYTOSIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSCRIPTION INITIATION; ACTIVE TRANSPORT; ANIMAL; CANCER TRANSPLANTATION; ENERGY METABOLISM; FEMALE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HOMEOSTASIS; METABOLISM; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; TUMOR CELL LINE; XENOGRAFT;

ACTIVE TRANSPORT, CELL NUCLEUS; AMINO ACIDS; ANIMALS; AUTOPHAGY; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; ENERGY METABOLISM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HETEROGRAFTS; HOMEOSTASIS; HUMANS; LYSOSOMES; MICE; MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR; NEOPLASM TRANSPLANTATION; PANCREATIC NEOPLASMS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84939787271     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature14587     Document Type: Article

References (50)

1. White, E. Exploiting the bad eating habits of Ras-driven cancers. Genes Dev. 27, 2065-2071 (2013).
2. Yang, S. et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 25, 717-729 (2011).
3. Rosenfeldt, M. T. et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature 504, 296-300 (2013).
4. Yang, A. et al. Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discov 4, 905-913 (2014).
5. Kroemer, G., Marino, G.& Levine, B. Autophagy and the integrated stress response. Mol. Cell 40, 280-293 (2010).
6. Haq, R.& Fisher, D. E. Biology and clinical relevance of the micropthalmia family of transcription factors in human cancer. J. Clin. Oncol. 29, 3474-3482 (2011).
7. Settembre, C. et al. TFEB links autophagy to lysosomal biogenesis. Science 332, 1429-1433 (2011).
8. Sardiello, M. et al. A gene network regulating lysosomal biogenesis and function. Science 325, 473-477 (2009).
9. Settembre, C. et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31, 1095-1108 (2012).
10. Roczniak-Ferguson, A. et al. The transcription factor TFEB linksmTORC1 signaling to transcriptional control of lysosome homeostasis. Sci. Signal. 5, ra42 (2012).
11. Martina, J. A. et al. The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci. Signal. 7, ra9 (2014).
12. Ting, L., Rad, R., Gygi, S. P. & Haas, W. MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics. Nature Methods 8, 937-940 (2011).
13. Raices, M.&D'Angelo, M. A. Nuclear pore complex composition: a newregulator of tissue-specific and developmental functions. Nature Rev. Mol. Cell Biol.
14. Chook, Y. M. & Suel, K. E. Nuclear import by karyopherin-bs: recognition and inhibition. Biochim. Biophys. Acta 1813, 1593-1606 (2011).
15. Zehorai, E. & Seger, R. Beta-like importins mediate the nuclear translocation of mitogen-activated protein kinases. Mol. Cell. Biol. 34, 259-270 (2014).
16. Yao, X., Chen, X., Cottonham, C.&Xu, L.Preferential utilization of Imp7/8 in nuclear import of Smads. J. Biol. Chem. 283, 22867-22874 (2008).
17. Waldmann, I.,Walde,S.&Kehlenbach,R.H.Nuclear import of c-Jun ismediatedby multiple transport receptors. J. Biol. Chem. 282, 27685-27692 (2007).
18. Xu, L. et al. Msk is required for nuclear import of TGF-b/BMP-activated Smads. J. Cell Biol. 178, 981-994 (2007).
19. Golomb, L. et al. Importin 7 and exportin 1 link c-Myc and p53 to regulation of ribosomal biogenesis. Mol. Cell 45, 222-232 (2012).
20. Ballabio, A. & Gieselmann, V. Lysosomal disorders: from storage to cellular damage. Biochim. Biophys. Acta 1793, 684-696 (2009).
21. Settembre, C., Fraldi, A., Medina, D. L. & Ballabio, A. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nature Rev. Mol. Cell Biol. 14, 283-296 (2013).
22. Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633-637 (2013).
23. Rabinowitz, J. D. & White, E. Autophagy and metabolism. Science 330, 1344-1348 (2010).
24. Singh, R. et al. Autophagy regulates lipid metabolism. Nature 458, 1131-1135 (2009).
25. Zoncu, R., Efeyan, A. & Sabatini, D. M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Rev. Mol. Cell Biol. 12, 21-35 (2011).
26. Petersen, N. H. et al. Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. Cancer Cell 24, 379-393 (2013).
27. Saftig, P. & Sandhoff, K. Cancer: killing from the inside. Nature 502, 312-313 (2013).
28. Narita, M. et al. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science 332, 966-970 (2011).
29. Tzatsos, A. et al. KDM2B promotes pancreatic cancer via Polycomb-dependent and-independent transcriptional programs. J. Clin. Invest. 123, 727-739 (2013).
30. Garraway, L. A. et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436, 117-122 (2005).
31. Gameiro, P. A. et al. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 17, 372-385 (2013).
32. Metallo,C.M. et al.Reductive glutaminemetabolismby IDH1mediates lipogenesis under hypoxia. Nature 481, 380-384 (2012).
33. Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633-637 (2013).
34. Steinberg, B. E. et al. A cation counterflux supports lysosomal acidification. J. Cell Biol. 189, 1171-1186 (2010).
35. Zoncu, R. et al. mTORC1 senses lysosomal amino acids through an inside-out mechanismthat requires the vacuolarH1-ATPase. Science 334, 678-683 (2011).
36. Hershey, C. L. & Fisher, D. E. Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform. Gene 347, 73-82 (2005).
37. Settembre, C. et al. TFEB links autophagy to lysosomal biogenesis. Science 332, 1429-1433 (2011).
38. Corcoran, R. B. et al. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res. 71, 5020-5029 (2011).
39. Chapel, A. et al. An extended proteome map of the lysosomal membrane reveals novel potential transporters. Mol. Cell. Proteomics 12, 1572-1588 (2013).
40. Schröder, B. et al. Integral and associated lysosomalmembrane proteins. Traffic 8, 1676-1686 (2007).
41. Behrends, C., Sowa, M. E., Gygi, S. P. & Harper, J. W. Network organization of the human autophagy system. Nature 466, 68-76 (2010).
42. Ballabio, A. & Gieselmann, V. Lysosomal disorders: from storage to cellular damage. Biochim. Biophys. Acta 1793, 684-696 (2009).
43. Huang,D.W., Sherman, B.T.&Lempicki,R.A.Systematic andintegrative analysis of large gene lists using DAVID Bioinformatics Resources. Nature Protoc. 4, 44-57 (2009).
44. Ting, L., Rad, R., Gygi, S. P. & Haas, W. MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics. Nature Methods 8, 937-940 (2011).
45. McAlister, G. C. et al. Increasing the multiplexing capacity of TMTs using reporter ion isotopologues with isobaric masses. Anal. Chem. 84, 7469-7478 (2012).
46. Weekes, M. P. et al. Quantitative temporal viromics: an approach to investigate host-pathogen interaction. Cell 157, 1460-1472 (2014).
47. Eng, J. K., McCormack, A. L. & Yates, J. R. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 5, 976-989 (1994).
48. Elias, J. E. & Gygi, S. P. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nature Methods 4, 207-214 (2007).
49. Huttlin, E. L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-1189 (2010).
50. Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-1806 (2008).