1932

Abstract

Cancer cells have an increased demand for energy sources to support accelerated rates of growth. When nutrients become limiting, cancer cells may switch to nonconventional energy sources that are mobilized through nutrient scavenging pathways involving autophagy and the lysosome. Thus, several cancers are highly reliant on constitutive activation of these pathways to degrade and recycle cellular materials. Here, we focus on the MiT/TFE family of transcription factors, which control transcriptional programs for autophagy and lysosome biogenesis and have emerged as regulators of energy metabolism in cancer. These new findings complement earlier reports that chromosomal translocations and amplifications involving the MiT/TFE genes contribute to the etiology and pathophysiology of renal cell carcinoma, melanoma, and sarcoma, suggesting pleiotropic roles for these factors in a wider array of cancers. Understanding the interplay between the oncogenic and stress-adaptive roles of MiT/TFE factors could shed light on fundamental mechanisms of cellular homeostasis and point to new strategies for cancer treatment.

Keyword(s): autophagylysosomeMITFmTORC1TFE3TFEB
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2019-03-04
2024-06-20
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Literature Cited

  1. Amin MB, Amin MB, Tamboli P, Javidan J, Stricker H et al. 2002. Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases. Am. J. Surg. Pathol. 26:3281–91
    [Google Scholar]
  2. Andrews NW, de Almeida PE, Corrotte M 2014. Damage control: cellular mechanisms of plasma membrane repair. Trends Cell Biol 24:12734–42
    [Google Scholar]
  3. Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF et al. 2001. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma. Am. J. Pathol. 159:1179–92
    [Google Scholar]
  4. Argani P, Hicks J, De Marzo AM, Albadine R, Illei PB et al. 2010. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am. J. Surg. Pathol. 34:91295–303
    [Google Scholar]
  5. Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M 2003.a Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am. J. Surg. Pathol. 27:6750–61
    [Google Scholar]
  6. Argani P, Lui MY, Couturier J, Bouvier R, Fournet J-C, Ladanyi M 2003.b A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene 22:345374–78
    [Google Scholar]
  7. Azizi AA, Haberler C, Czech T, Gupper A, Prayer D et al. 2006. Vascular-endothelial-growth-factor (VEGF) expression and possible response to angiogenesis inhibitor bevacizumab in metastatic alveolar soft part sarcoma. Lancet Oncol 7:6521–23
    [Google Scholar]
  8. Beckmann H, Su LK, Kadesch T 1990. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer μE3 motif. Genes Dev 4:2167–79
    [Google Scholar]
  9. Bertolotto C, Lesueur F, Giuliano S, Strub T, de Lichy M et al. 2011. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 480:737594–98
    [Google Scholar]
  10. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L et al. 2001. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:55471704–8
    [Google Scholar]
  11. Boone BA, Bahary N, Zureikat AH, Moser AJ, Normolle DP et al. 2015. Safety and biologic response of pre-operative autophagy inhibition in combination with gemcitabine in patients with pancreatic adenocarcinoma. Ann. Surg. Oncol. 22:134402–10
    [Google Scholar]
  12. Bruder E, Passera O, Harms D, Leuschner I, Ladanyi M et al. 2004. Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am. J. Surg. Pathol. 28:91117–32
    [Google Scholar]
  13. Buerger C, DeVries B, Stambolic V 2006. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem. Biophys. Res. Commun. 344:3869–80
    [Google Scholar]
  14. Buscà R, Berra E, Gaggioli C, Khaled M, Bille K et al. 2005. Hypoxia-inducible factor 1α is a new target of microphthalmia-associated transcription factor (MITF) in melanoma cells. J. Cell Biol. 170:149–49
    [Google Scholar]
  15. Cadwell K, Debnath J 2018. Beyond self-eating: the control of nonautophagic functions and signaling pathways by autophagy-related proteins. J. Cell Biol. 217:3813–22
    [Google Scholar]
  16. Calcagnì A, Kors L, Verschuren E, De Cegli R, Zampelli N et al. 2016. Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling. eLife 5:e17047
    [Google Scholar]
  17. Cancer Genome Atlas Res. Netw. 2013. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:745643–49
    [Google Scholar]
  18. Cancer Genome Atlas Res. Netw. 2015. Genomic classification of cutaneous melanoma. Cell 161:71681–1681
    [Google Scholar]
  19. Cancer Genome Atlas Res. Netw. 2016. Comprehensive molecular characterization of papillary renal-cell carcinoma. N. Engl. J. Med. 374:2135–45
    [Google Scholar]
  20. Cheng X, Zhang X, Gao Q, Ali Samie M, Azar M et al. 2014. The intracellular Ca2+ channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy. Nat. Med. 20:101187–92
    [Google Scholar]
  21. Cheng X, Zhang X, Yu L, Xu H 2015. Calcium signaling in membrane repair. Semin. Cell Dev. Biol. 45:24–31
    [Google Scholar]
  22. Clark J, Lu YJ, Sidhar SK, Parker C, Gill S et al. 1997. Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. Oncogene 15:182233–39
    [Google Scholar]
  23. Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ et al. 2013. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:7451633–37
    [Google Scholar]
  24. Conner SD, Schmid SL 2003. Regulated portals of entry into the cell. Nature 422:692737–44
    [Google Scholar]
  25. Cronin JC, Wunderlich J, Loftus SK, Prickett TD, Wei X et al. 2009. Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res 22:4435–44
    [Google Scholar]
  26. Davidson SM, Jonas O, Keibler MA, Hou HW, Luengo A et al. 2017. Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat. Med. 23:2235–41
    [Google Scholar]
  27. Davidson SM, Papagiannakopoulos T, Olenchock BA, Heyman JE, Keibler MA et al. 2016. Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer. Cell Metab 23:3517–28
    [Google Scholar]
  28. Davies H, Bignell GR, Cox C, Stephens P, Edkins S et al. 2002. Mutations of the BRAF gene in human cancer. Nature 417:6892949–54
    [Google Scholar]
  29. Davis IJ, Hsi B-L, Arroyo JD, Vargas SO, Yeh YA et al. 2003. Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. PNAS 100:106051–56
    [Google Scholar]
  30. de Duve C. 2005. The lysosome turns fifty. Nat. Cell Biol. 7:9847–49
    [Google Scholar]
  31. De Palma M, Biziato D, Petrova TV 2017. Microenvironmental regulation of tumour angiogenesis. Nat. Rev. Cancer 17:8457–74
    [Google Scholar]
  32. DeNicola GM, Cantley LC 2015. Cancer's fuel choice: new flavors for a picky eater. Mol. Cell. 60:4514–23
    [Google Scholar]
  33. Di Fiore PP, von Zastrow M 2014. Endocytosis, signaling, and beyond. Cold Spring Harb. Perspect. Biol. 6:8a016865
    [Google Scholar]
  34. Di Malta C, Siciliano D, Calcagni A, Monfregola J, Punzi S et al. 2017. Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth. Science 356:63431188–92
    [Google Scholar]
  35. Eddy RJ, Weidmann MD, Sharma VP, Condeelis JS 2017. Tumor cell invadopodia: invasive protrusions that orchestrate metastasis. Trends Cell Biol 27:8595–607
    [Google Scholar]
  36. Ennen M, Keime C, Kobi D, Mengus G, Lipsker D et al. 2015. Single-cell gene expression signatures reveal melanoma cell heterogeneity. Oncogene 34:253251–63
    [Google Scholar]
  37. Fan Y, Lu H, Liang W, Garcia-Barrio MT, Guo Y et al. 2018. Endothelial TFEB (transcription factor EB) positively regulates postischemic angiogenesis. Circ. Res. 122:7945–57
    [Google Scholar]
  38. Farley MN, Schmidt LS, Mester JL, Pena-Llopis S, Pavia-Jimenez A et al. 2013. A novel germline mutation in BAP1 predisposes to familial clear-cell renal cell carcinoma. Mol. Cancer Res. 11:91061–71
    [Google Scholar]
  39. Ferron M, Settembre C, Shimazu J, Lacombe J, Kato S et al. 2013. A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes Dev 27:8955–69
    [Google Scholar]
  40. Ghose A, Tariq Z, Veltri S 2012. Treatment of multidrug resistant advanced alveolar soft part sarcoma with sunitinib. Am. J. Ther. 19:1e56–58
    [Google Scholar]
  41. Goldstein JL, Brown MS 2015. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 161:1161–72
    [Google Scholar]
  42. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL 2001. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. PNAS 98:2514440–45
    [Google Scholar]
  43. Goodwin ML, Jin H, Straessler K, Smith-Fry K, Zhu J-F et al. 2014. Modeling alveolar soft part sarcomagenesis in the mouse: a role for lactate in the tumor microenvironment. Cancer Cell 26:6851–62
    [Google Scholar]
  44. Guo JY, Chen H-Y, Mathew R, Fan J, Strohecker AM et al. 2011. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:5460–70
    [Google Scholar]
  45. Guo JY, Teng X, Laddha SV, Ma S, Van Nostrand SC et al. 2016. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells. Genes Dev 30:151704–17
    [Google Scholar]
  46. Haq R, Fisher DE 2011. Biology and clinical relevance of the micropthalmia family of transcription factors in human cancer. J. Clin. Oncol. 29:253474–82
    [Google Scholar]
  47. Heckmann BL, Boada-Romero E, Cunha LD, Magne J, Green DR 2017. LC3-associated phagocytosis and inflammation. J. Mol. Biol. 429:233561–76
    [Google Scholar]
  48. Hemesath TJ, Steingrímsson E, McGill G, Hansen MJ, Vaught J et al. 1994. Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev 8:222770–80
    [Google Scholar]
  49. Hershey CL, Fisher DE 2004. Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function. Bone 34:4689–96
    [Google Scholar]
  50. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M et al. 2012. A landscape of driver mutations in melanoma. Cell 150:2251–63
    [Google Scholar]
  51. Hoek KS, Eichhoff OM, Schlegel NC, Döbbeling U, Kobert N et al. 2008. In vivo switching of human melanoma cells between proliferative and invasive states. Cancer Res 68:3650–56
    [Google Scholar]
  52. Huo Y, Cai H, Teplova I, Bowman-Colin C, Chen G et al. 2013. Autophagy opposes p53-mediated tumor barrier to facilitate tumorigenesis in a model of PALB2-associated hereditary breast cancer. Cancer Discov 3:8894–907
    [Google Scholar]
  53. Ilagan E, Manning BD 2016. Emerging role of mTOR in the response to cancer therapeutics. Trends Cancer 2:5241–51
    [Google Scholar]
  54. Jimenez AJ, Perez F 2017. Plasma membrane repair: the adaptable cell life-insurance. Curr. Opin. Cell Biol. 47:99–107
    [Google Scholar]
  55. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R et al. 2013. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. PNAS 110:228882–87
    [Google Scholar]
  56. Kamphorst JJ, Nofal M, Commisso C, Hackett SR, Lu W et al. 2015. Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res 75:3544–53
    [Google Scholar]
  57. Kaneko T, Zhang Z, Mantellini MG, Karl E, Zeitlin B et al. 2007. Bcl-2 orchestrates a cross-talk between endothelial and tumor cells that promotes tumor growth. Cancer Res 67:209685–93
    [Google Scholar]
  58. Karsli-Uzunbas G, Guo JY, Price S, Teng X, Laddha SV et al. 2014. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov 4:8914–27
    [Google Scholar]
  59. Kauffman EC, Ricketts CJ, Rais-Bahrami S, Yang Y, Merino MJ et al. 2014. Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers. Nat. Rev. Urol. 11:8465–75
    [Google Scholar]
  60. Kaur J, Debnath J 2015. Autophagy at the crossroads of catabolism and anabolism. Nat. Rev. Mol. Cell Biol. 16:8461–72
    [Google Scholar]
  61. Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan K-L 2008. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10:8935–45
    [Google Scholar]
  62. Kitamura Y, Morii E, Jippo T, Ito A 2002. Regulation of mast cell phenotype by MITF. Int. Arch. Allergy Immunol. 127:2106–9
    [Google Scholar]
  63. Kobos R, Nagai M, Tsuda M, Merl MY, Saito T et al. 2013. Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein. J. Pathol. 229:5743–54
    [Google Scholar]
  64. Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA et al. 2014. A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4:7816–27
    [Google Scholar]
  65. Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E et al. 2003. Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. Hum. Mol. Genet. 12:141661–69
    [Google Scholar]
  66. Lazar AJF, Das P, Tuvin D, Korchin B, Zhu Q et al. 2007. Angiogenesis-promoting gene patterns in alveolar soft part sarcoma. Clin. Cancer Res. 13:247314–21
    [Google Scholar]
  67. Leeman DS, Hebestreit K, Ruetz T, Webb AE, McKay A et al. 2018. Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging. Science 359:63811277–83
    [Google Scholar]
  68. Levine B, Deretic V 2007. Unveiling the roles of autophagy in innate and adaptive immunity. Nat. Rev. Immunol. 7:10767–77
    [Google Scholar]
  69. Linehan WM, Ricketts CJ 2013. The metabolic basis of kidney cancer. Semin. Cancer Biol. 23:146–55
    [Google Scholar]
  70. Linehan WM, Srinivasan R, Schmidt LS 2010. The genetic basis of kidney cancer: a metabolic disease. Nat. Rev. Urol. 7:5277–85
    [Google Scholar]
  71. Lock R, Roy S, Kenific CM, Su JS, Salas E et al. 2011. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol. Biol. Cell. 22:2165–78
    [Google Scholar]
  72. Lunt SY, Vander Heiden MG 2011. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27:441–64
    [Google Scholar]
  73. Lyssiotis CA, Kimmelman AC 2017. Metabolic interactions in the tumor microenvironment. Trends Cell Biol 27:11863–75
    [Google Scholar]
  74. Mahalingam D, Mita M, Sarantopoulos J, Wood L, Amaravadi RK et al. 2014. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy 10:81403–14
    [Google Scholar]
  75. Maitra A, Hruban RH 2008. Pancreatic cancer. Annu. Rev. Pathol. 3:157–88
    [Google Scholar]
  76. Mansueto G, Armani A, Viscomi C, D'Orsi L, De Cegli R et al. 2017. Transcription factor EB controls metabolic flexibility during exercise. Cell Metab 25:1182–96
    [Google Scholar]
  77. Marchand B, Arsenault D, Raymond-Fleury A, Boisvert F-M, Boucher M-J 2015. Glycogen synthase kinase-3 (GSK3) inhibition induces prosurvival autophagic signals in human pancreatic cancer cells. J. Biol. Chem. 290:95592–605
    [Google Scholar]
  78. Martina JA, Chen Y, Gucek M, Puertollano R 2012. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8:6903–14
    [Google Scholar]
  79. Martina JA, Diab HI, Lishu L, Jeong-A L, Patange S et al. 2014. The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci. Signal. 7:309ra9
    [Google Scholar]
  80. McAfee Q, Zhang Z, Samanta A, Levi SM, Ma X-H et al. 2012. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. PNAS 109:218253–58
    [Google Scholar]
  81. McGill GG, Horstmann M, Widlund HR, Du J, Motyckova G et al. 2002. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109:6707–18
    [Google Scholar]
  82. Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D et al. 2015. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat. Cell Biol. 17:3288–99
    [Google Scholar]
  83. Medina DL, Fraldi A, Bouche V, Annunziata F, Mansueto G et al. 2011. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell. 21:3421–30
    [Google Scholar]
  84. Miller AJ, Levy C, Davis IJ, Razin E, Fisher DE 2005. Sumoylation of MITF and its related family members TFE3 and TFEB. J. Biol. Chem. 280:1146–55
    [Google Scholar]
  85. Mizushima N, Komatsu M 2011. Autophagy: renovation of cells and tissues. Cell 147:4728–41
    [Google Scholar]
  86. Monkkonen T, Debnath J 2018. Inflammatory signaling cascades and autophagy in cancer. Autophagy 14:2190–98
    [Google Scholar]
  87. Müller J, Krijgsman O, Tsoi J, Robert L, Hugo W et al. 2014. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat. Commun. 5:5712
    [Google Scholar]
  88. Naegeli KM, Hastie E, Garde A, Wang Z, Keeley DP et al. 2017. Cell invasion in vivo via rapid exocytosis of a transient lysosome-derived membrane domain. Dev. Cell. 43:4403–17.e10
    [Google Scholar]
  89. Napolitano G, Ballabio A 2016. TFEB at a glance. J. Cell Sci. 129:132475–81
    [Google Scholar]
  90. Olson OC, Joyce JA 2015. Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat. Rev. Cancer 15:12712–29
    [Google Scholar]
  91. O'Rourke EJ, Ruvkun G 2013. MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability. Nat. Cell Biol. 15:6668–76
    [Google Scholar]
  92. Palm W, Park Y, Wright K, Pavlova NN, Tuveson DA et al. 2015. The utilization of extracellular proteins as nutrients is suppressed by mTORC1. Cell 162:2259–70
    [Google Scholar]
  93. Palmieri M, Impey S, Kang H, di Ronza A, Pelz C et al. 2011. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Genet. 20:193852–66
    [Google Scholar]
  94. Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, Leng N, Pavía-Jiménez A et al. 2012. BAP1 loss defines a new class of renal cell carcinoma. Nat. Genet. 44:7751–59
    [Google Scholar]
  95. Peña-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC, Wolff NC, Tran TAT et al. 2011. Regulation of TFEB and V-ATPases by mTORC1. EMBO J 30:163242–58
    [Google Scholar]
  96. Perera RM, Bardeesy N 2015. Pancreatic cancer metabolism: breaking it down to build it back up. Cancer Discov 5:121247–61
    [Google Scholar]
  97. Perera RM, Stoykova S, Nicolay BN, Ross KN, Fitamant J et al. 2015. Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature 524:7565361–65
    [Google Scholar]
  98. Piao S, Amaravadi RK 2016. Targeting the lysosome in cancer. Ann. N.Y. Acad. Sci. 1371:145–54
    [Google Scholar]
  99. Ploper D, Taelman VF, Robert L, Perez BS, Titz B et al. 2015. MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells. PNAS 112:5E420–29
    [Google Scholar]
  100. Polishchuk EV, Concilli M, Iacobacci S, Chesi G, Pastore N et al. 2014. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev. Cell. 29:6686–700
    [Google Scholar]
  101. Potente M, Gerhardt H, Carmeliet P 2011. Basic and therapeutic aspects of angiogenesis. Cell 146:6873–87
    [Google Scholar]
  102. Qi X, Hong J, Chaves L, Zhuang Y, Chen Y et al. 2013. Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates. Immunity 39:197–110
    [Google Scholar]
  103. Rabinowitz JD, White E 2010. Autophagy and metabolism. Science 330:60091344–48
    [Google Scholar]
  104. Ramphal R, Pappo A, Zielenska M, Grant R, Ngan B-Y 2006. Pediatric renal cell carcinoma: clinical, pathologic, and molecular abnormalities associated with the members of the MiT transcription factor family. Am. J. Clin. Pathol. 126:3349–64
    [Google Scholar]
  105. Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM et al. 2014. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy 10:81369–79
    [Google Scholar]
  106. Rao S, Tortola L, Perlot T, Wirnsberger G, Novatchkova M et al. 2014. A dual role for autophagy in a murine model of lung cancer. Nat. Commun. 5:3056
    [Google Scholar]
  107. Rebecca VW, Nicastri MC, McLaughlin N, Fennelly C, McAfee Q et al. 2017. A unified approach to targeting the lysosome's degradative and growth signaling roles. Cancer Discov 7:111266–83
    [Google Scholar]
  108. Reddy A, Caler EV, Andrews NW 2001. Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes. Cell 106:2157–69
    [Google Scholar]
  109. Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J et al. 2012. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci. Signal. 5:228ra42
    [Google Scholar]
  110. Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C et al. 2016. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature 534:7606272–76
    [Google Scholar]
  111. Ryan DP, Hong TS, Bardeesy N 2014. Pancreatic adenocarcinoma. N. Engl. J. Med. 371:111039–49
    [Google Scholar]
  112. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:2290–303
    [Google Scholar]
  113. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC et al. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:58821496–501
    [Google Scholar]
  114. Sánchez-Gastaldo A, Kempf E, González Del Alba A, Duran I 2017. Systemic treatment of renal cell cancer: a comprehensive review. Cancer Treat. Rev. 60:77–89
    [Google Scholar]
  115. Sandri M. 2016. Protein breakdown in cancer cachexia. Semin. Cell Dev. Biol. 54:11–19
    [Google Scholar]
  116. Santanam U, Banach-Petrosky W, Abate-Shen C, Shen MM, White E, DiPaola RS 2016. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth. Genes Dev 30:4399–407
    [Google Scholar]
  117. Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M et al. 2009. A gene network regulating lysosomal biogenesis and function. Science 325:5939473–77
    [Google Scholar]
  118. Sato S, Roberts K, Gambino G, Cook A, Kouzarides T, Goding CR 1997. CBP/p300 as a co-factor for the Microphthalmia transcription factor. Oncogene 14:253083–92
    [Google Scholar]
  119. Saxton RA, Sabatini DM 2017. mTOR signaling in growth, metabolism, and disease. Cell 169:2361–71
    [Google Scholar]
  120. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G et al. 1997. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat. Genet. 16:168–73
    [Google Scholar]
  121. Schürmann A, Brauers A, Massmann S, Becker W, Joost HG 1995. Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J. Biol. Chem. 270:4828982–88
    [Google Scholar]
  122. Sekiguchi T, Hirose E, Nakashima N, Ii M, Nishimoto T 2001. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J. Biol. Chem. 276:107246–57
    [Google Scholar]
  123. Settembre C, Ballabio A 2014. Lysosome: regulator of lipid degradation pathways. Trends Cell Biol 24:12743–50
    [Google Scholar]
  124. Settembre C, De Cegli R, Mansueto G, Saha PK, Vetrini F et al. 2013.a TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat. Cell Biol. 15:6647–58
    [Google Scholar]
  125. Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F et al. 2011. TFEB links autophagy to lysosomal biogenesis. Science 332:60361429–33
    [Google Scholar]
  126. Settembre C, Fraldi A, Medina DL, Ballabio A 2013.b Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 14:5283–96
    [Google Scholar]
  127. Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S et al. 2012. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB: self-regulation of the lysosome via mTOR and TFEB. EMBO J 31:51095–108
    [Google Scholar]
  128. Shibahara S, Yasumoto K, Amae S, Udono T, Watanabe K et al. 2000. Regulation of pigment cell-specific gene expression by MITF. Pigment Cell Res 13:Suppl. 898–102
    [Google Scholar]
  129. Shipley JM, Birdsall S, Clark J, Crew J, Gill S et al. 1995. Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case. Cytogenet. Cell Genet. 71:3280–84
    [Google Scholar]
  130. Sidhar SK, Clark J, Gill S, Hamoudi R, Crew AJ et al. 1996. The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum. Mol. Genet. 5:91333–38
    [Google Scholar]
  131. Stacchiotti S, Tamborini E, Marrari A, Brich S, Rota SA et al. 2009. Response to sunitinib malate in advanced alveolar soft part sarcoma. Clin. Cancer Res. 15:31096–1104
    [Google Scholar]
  132. Steingrímsson E, Copeland NG, Jenkins NA 2004. Melanocytes and the microphthalmia transcription factor network. Annu. Rev. Genet. 38:365–411
    [Google Scholar]
  133. Steingrímsson E, Moore KJ, Lamoreux ML, Ferré-D'Amaré AR, Burley SK et al. 1994. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nat. Genet. 8:3256–63
    [Google Scholar]
  134. Steingrímsson E, Tessarollo L, Pathak B, Hou L, Arnheiter H et al. 2002. Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. PNAS 99:74477–82
    [Google Scholar]
  135. Steingrímsson E, Tessarollo L, Reid SW, Jenkins NA, Copeland NG 1998. The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. Development 125:234607–16
    [Google Scholar]
  136. Strohecker AM, Guo JY, Karsli-Uzunbas G, Price SM, Chen GJ et al. 2013. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer Discov 3:111272–85
    [Google Scholar]
  137. Subramani S, Malhotra V 2013. Non-autophagic roles of autophagy-related proteins. EMBO Rep 14:2143–51
    [Google Scholar]
  138. Tachibana M, Takeda K, Nobukuni Y, Urabe K, Long JE et al. 1996. Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. Nat. Genet. 14:150–54
    [Google Scholar]
  139. Tanaka M, Homme M, Yamazaki Y, Shimizu R, Takazawa Y, Nakamura T 2017. Modeling alveolar soft part sarcoma unveils novel mechanisms of metastasis. Cancer Res 77:4897–907
    [Google Scholar]
  140. Tanaka M, Kato K, Gomi K, Matsumoto M, Kudo H et al. 2009. Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma. Am. J. Surg. Pathol. 33:91416–20
    [Google Scholar]
  141. Tirosh I, Izar B, Prakadan SM, Wadsworth MH, Treacy D et al. 2016. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352:6282189–96
    [Google Scholar]
  142. Trisciuoglio D, Gabellini C, Desideri M, Ragazzoni Y, De Luca T et al. 2011. Involvement of BH4 domain of bcl-2 in the regulation of HIF-1-mediated VEGF expression in hypoxic tumor cells. Cell Death Differ 18:61024–35
    [Google Scholar]
  143. Tsao H, Chin L, Garraway LA, Fisher DE 2012. Melanoma: from mutations to medicine. Genes Dev 26:111131–55
    [Google Scholar]
  144. Vogl DT, Stadtmauer EA, Tan K-S, Heitjan DF, Davis LE et al. 2014. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy 10:81380–90
    [Google Scholar]
  145. Wei H, Wei S, Gan B, Peng X, Zou W, Guan J-L 2011. Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev 25:141510–27
    [Google Scholar]
  146. Weterman MA, Wilbrink M, Geurts van Kessel A 1996. Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. PNAS 93:2615294–98
    [Google Scholar]
  147. Weterman MJ, van Groningen JJ, Jansen A, van Kessel AG 2000. Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins. Oncogene 19:169–74
    [Google Scholar]
  148. White E. 2015. The role for autophagy in cancer. J. Clin. Investig. 125:142–46
    [Google Scholar]
  149. Xie X, Koh JY, Price S, White E, Mehnert JM 2015. Atg7 overcomes senescence and promotes growth of BrafV600E-driven melanoma. Cancer Discov 5:4410–23
    [Google Scholar]
  150. Xu Q, Krause M, Samoylenko A, Vainio S 2016. Wnt signaling in renal cell carcinoma. Cancers 8:657
    [Google Scholar]
  151. Yang A, Herter-Sprie G, Zhang H, Lin EY, Biancur D et al. 2018. Autophagy sustains pancreatic cancer growth through both cell-autonomous and nonautonomous mechanisms. Cancer Discov 8:3276–87
    [Google Scholar]
  152. Yang A, Rajeshkumar NV, Wang X, Yabuuchi S, Alexander BM et al. 2014. Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discov 4:8905–13
    [Google Scholar]
  153. Yang R, Zheng Y, Li L, Liu S, Burrows M et al. 2014. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat. Commun. 5:5807
    [Google Scholar]
  154. Yang S, Wang X, Contino G, Liesa M, Sahin E et al. 2011. Pancreatic cancers require autophagy for tumor growth. Genes Dev 25:7717–29
    [Google Scholar]
  155. Yecies JL, Manning BD 2011. mTOR links oncogenic signaling to tumor cell metabolism. J. Mol. Med. 89:3221–28
    [Google Scholar]
  156. Ying H, Dey P, Yao W, Kimmelman AC, Draetta GF et al. 2016. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev 30:4355–85
    [Google Scholar]
  157. Yokoyama S, Woods SL, Boyle GM, Aoude LG, MacGregor S et al. 2011. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480:737599–103
    [Google Scholar]
  158. Zhou Y, Tang F, Wang Y, Min L, Luo Y et al. 2017. Advanced alveolar soft part sarcoma responds to apatinib. Oncotarget 8:3050314–22
    [Google Scholar]
  159. Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM 2011. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H+-ATPase. Science 334:6056678–83
    [Google Scholar]
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