Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 30, 2011, Pages 12455-12460

  Parkhitko, Andrey ^a,b   Myachina, Faina ^a   Morrison, Tasha A ^a   Hindi, Khadijah M ^a   Auricchio, Neil ^a   Karbowniczek, Magdalena ^c   Wu, J Julia ^d   Finkel, Toren ^d   Kwiatkowski, David J ^a   Yu, Jane J ^a   Henske, Elizabeth Petri ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY   (Russian Federation)

^c TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^d NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

Cell survival; Chloroquine; Metabolism; Therapy

Indexed keywords

AUTOPHAGY PROTEIN 5; BECLIN 1; CHLOROQUINE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PROTEIN P62; RAPAMYCIN; SEQUESTOSOME 1; TUBERIN; UNCLASSIFIED DRUG;

ALLELE; ANGIOMYOLIPOMA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER INHIBITION; CARCINOGENESIS; CELL SURVIVAL; CONTROLLED STUDY; CYSTADENOMA; DOWN REGULATION; DRUG DOSE COMPARISON; DRUG POTENTIATION; GENE DISRUPTION; GENOTYPE; HETEROZYGOTE; HUMAN; HUMAN TISSUE; KIDNEY TUMOR; MOUSE; NONHUMAN; PRIORITY JOURNAL; SURVIVAL; TUBEROUS SCLEROSIS; TUMOR CELL; TUMOR NECROSIS; TUMOR XENOGRAFT;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; CELL SURVIVAL; GENES, P53; HEAT-SHOCK PROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, NUDE; MICE, SCID; MICROTUBULE-ASSOCIATED PROTEINS; PROTEINS; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

MAMMALIA; MUS;

EID: 79961059959     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1104361108     Document Type: Article

References (50)

1. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27-42.
2. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069-1075. (Pubitemid 351317450)
3. McPhee CK, Logan MA, Freeman MR, Baehrecke EH (2010) Activation of autophagy during cell death requires the engulfment receptor Draper. Nature 465:1093-1096.
4. Rabinowitz JD, White E (2010) Autophagy and metabolism. Science 330:1344-1348.
5. Solomon VR, Lee H (2009) Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol 625: 220-233.
6. Amaravadi RK, et al. (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326-336. (Pubitemid 46203961)
7. Qu X, et al. (2003) Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 112:1809-1820. (Pubitemid 38063704)
8. Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 100:15077-15082. (Pubitemid 37518019)
9. Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345-1356.
10. Manning BD, Cantley LC (2007) AKT/PKB signaling: Navigating downstream. Cell 129: 1261-1274. (Pubitemid 46962095)
11. Brugarolas J, Kaelin WG, Jr. (2004) Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes. Cancer Cell 6:7-10. (Pubitemid 38903157)
12. Brugarolas J, et al. (2004) Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18:2893-2904. (Pubitemid 39602308)
13. Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577-590. (Pubitemid 37506046)
14. Lee DF, et al. (2007) IKK-β suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell 130:440-455.
15. Astrinidis A, Senapedis W, Coleman TR, Henske EP (2003) Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B. J Biol Chem 278:51372-51379. (Pubitemid 38020376)
16. Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122:3589-3594.
17. Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10:307-318.
18. Hosokawa N, et al. (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20:1981-1991.
19. Ganley IG, et al. (2009) ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 284:12297-12305.
20. Chang YY, Neufeld TP (2009) An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell 20:2004-2014.
21. Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ (1999) Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 104:687-695. (Pubitemid 29536354)
22. Kabeya Y, et al. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720-5728.
23. Bjørkøy G, et al. (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171: 603-614. (Pubitemid 41668720)
24. Howe SR, et al. (1995) Rodent model of reproductive tract leiomyomata: Establishment and characterization of tumor-derived cell lines. Am J Pathol 146:1568-1579.
25. Fedorko M (1967) Effect of chloroquine on morphology of cytoplasmic granules in maturing human leukocytes: An ultrastructural study. J Clin Invest 46:1932-1942.
26. +/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis-related tumors. J Transl Med 8(14):1-18.
27. Buhaescu I, Izzedine H, Covic A (2006) Sirolimus - challenging current perspectives. Ther Drug Monit 28:577-584. (Pubitemid 44564052)
28. Kuma A, et al. (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032-1036. (Pubitemid 40052234)
29. Mizushima N, et al. (1998) A protein conjugation system essential for autophagy. Nature 395:395-398. (Pubitemid 28450691)
30. Mathew R, et al. (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 21:1367-1381. (Pubitemid 46871040)
31. Degenhardt K, et al. (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51-64.
32. Guo JY, et al. (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:460-470.
33. Lee L, et al. (2005) Efficacy of a rapamycin analog (CCI-779) and IFN-γ in tuberous sclerosis mouse models. Genes Chromosomes Cancer 42:213-227. (Pubitemid 40171186)
34. Pollizzi K, Malinowska-Kolodziej I, Stumm M, Lane H, Kwiatkowski D (2009) Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis. Mol Cancer 8(38):1-9.
35. Duran A, et al. (2008) The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis. Cancer Cell 13:343-354. (Pubitemid 351446193)
36. Mathew R, et al. (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062-1075.
37. Kondo Y, Kanzawa T, Sawaya R, Kondo S (2005) The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 5:726-734. (Pubitemid 41486365)
38. Mathew R, Karantza-Wadsworth V, White E (2007) Role of autophagy in cancer. Nat Rev Cancer 7:961-967. (Pubitemid 350165856)
39. Yu L, et al. (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465:942-946.
40. Choo AY, et al. (2010) Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell 38:487-499.
41. Düvel K, et al. (2010) Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 39:171-183.
42. Zhou X, et al. (2009) Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy. Proc Natl Acad Sci USA 106:8923-8928.
43. Alexander A, et al. (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA 107:4153-4158.
44. Li B, Gordon GM, Du CH, Xu J, DuW(2010) Specific killing of Rb mutant cancer cells by inactivating TSC2. Cancer Cell 17:469-480.
45. Komatsu M, et al. (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12:213-223.
46. Bissler JJ, et al. (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358:140-151.
47. Franz DN, et al. (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59:490-498. (Pubitemid 43358069)
48. Krueger DA, et al. (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363:1801-1811.
49. Onda H, et al. (2002) Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway. Mol Cell Neurosci 21:561-574. (Pubitemid 36062714)
50. Yu J, Astrinidis A, Howard S, Henske EP (2004) Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and non-genomic signaling pathways. Am J Physiol Lung Cell Mol Physiol 286:L694-L700. (Pubitemid 38365052)