Cancer-associated lysosomal changes: Friends or foes¿

Oncogene

Volumn 32, Issue 16, 2013, Pages 1995-2004

  Kallunki, T ^a   Olsen, O D ^a   Jaattela M ^a  

^a DANISH CANCER SOCIETY RESEARCH CENTER   (Denmark)

Author keywords

Cancer; cell death; Lysosome; metastasis

Indexed keywords

ACID CERAMIDASE; CATHEPSIN B; CATHEPSIN D; CATHEPSIN F; CATHEPSIN H; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; CATHEPSIN V; HEPARANASE; LYSOSOME ENZYME; NEU1 SIALIDASE 1; SIALIDASE; SPHINGOLIPID; SPHINGOMYELIN PHOSPHODIESTERASE; UNCLASSIFIED DRUG;

ANGIOGENESIS; AUTOPHAGY; BIOGENESIS; CANCER CELL; CANCER GROWTH; CELL DAMAGE; CELL SURVIVAL; CHEMICAL COMPOSITION; ENDOCYTOSIS; ENDOSOME; GOLGI COMPLEX; HUMAN; LIPOLYSIS; LYSOSOME; LYSOSOME MEMBRANE; METASTASIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN TARGETING; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; APOPTOSIS; CELL DEATH; HUMANS; LYSOSOMES; NEOPLASM METASTASIS; NEOPLASMS;

EID: 84876664386     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2012.292     Document Type: Review

References (152)

1. Kolter T, Sandhoff K. Lysosomal degradation of membrane lipids. FEBS Lett 2009; 584: 1700-1712.
2. Pryor PR, Luzio JP. Delivery of endocytosed membrane proteins to the lysosome. Biochim Biophys Acta 2009; 1793: 615-624.
3. Saftig P, Klumperman J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 2009; 10: 623-635.
4. Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 2006; 6: 764-775.
5. Palermo C, Joyce JA. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol Sci 2008; 29: 22-28.
6. Ilan N, Elkin M, Vlodavsky I. Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol 2006; 38: 2018-2039.
7. Kirkegaard T, Jäättelä M. Lysosomal involvement in cell death and cancer. Biochim Biophys Acta 2009; 1793: 746-754.
8. Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des 2007; 13: 387-403.
9. Kuester D, Lippert H, Roessner A, Krueger S. The cathepsin family and their role in colorectal cancer. Pathol Res Pract 2008; 204: 491-500.
10. Miao HQ, Liu H, Navarro E, Kussie P, Zhu Z. Development of heparanase inhibitors for anti-cancer therapy. Curr Med Chem 2006; 13: 2101-2111.
11. Groth-Pedersen L, Jäättelä M. Combating apoptosis and multidrug resistant cancers by targeting lysosomes. Cancer Lett (e-pub ahead of print 30 June 2010).
12. Braulke T, Bonifacino JS. Sorting of lysosomal proteins. Biochim Biophys Acta 2009; 1793: 605-614.
13. Hernandez A, Serrano G, Herrera-Palau R, Perez-Castineira JR, Serrano A. Intraorganellar acidification by V-ATPases: a target in cell proliferation and cancer therapy. Recent Pat Anticancer Drug Discov 2010; 5: 88-98.
14. Beyenbach KW, Wieczorek H. The V-type H + ATPase: molecular structure and function, physiological roles and regulation. J Exp Biol 2006; 209(Part 4): 577-589.
15. van der Goot FG, Gruenberg J. Intra-endosomal membrane traffic. Trends Cell Biol 2006; 16: 514-521.
16. Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X et al. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell 2007; 131: 770-783.
17. Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem 1997; 272: 3599-3605.
18. Ni X, Morales CR. The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor. Traffic 2006; 7: 889-902.
19. Kroemer G, Jäättelä M. Lysosomes and autophagy in cell death control. Nat Rev Cancer 2005; 5: 886-897.
20. Gerasimenko JV, Gerasimenko OV, Petersen OH. Membrane repair: Ca(2+)-elicited lysosomal exocytosis. Curr Biol 2001; 11: R971-R974.
21. Vasiljeva O, Turk B. Dual contrasting roles of cysteine cathepsins in cancer progression: apoptosis versus tumour invasion. Biochimie 2008; 90: 380-386.
22. van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 2008; 9: 112-124.
23. Mobius W, van Donselaar E, Ohno-Iwashita Y, Shimada Y, Heijnen HF, Slot JW et al. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic 2003; 4: 222-231.
24. Eskelinen EL, Tanaka Y, Saftig P. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol 2003; 13: 137-145.
25. Janvier K, Bonifacino JS. Role of the endocytic machinery in the sorting of lysosome-associated membrane proteins. Mol Biol Cell 2005; 16: 4231-4242.
26. Fehrenbacher N, Bastholm L, Kirkegaard-Sorensen T, Rafn B, Bottzauw T, Nielsen C et al. Sensitization to the lysosomal cell death pathway by oncogene-induced down-regulation of lysosome-associated membrane proteins 1 and 2. Cancer Res 2008; 68: 6623-6633.
27. Eskelinen EL. Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 2006; 27: 495-502.
28. Schneede A, Schmidt CK, Holtta-Vuori M, Heeren J, Willenborg M, Blanz J et al. Role for LAMP-2 in endosomal cholesterol transport. J Cell Mol Med 2011; 15: 280-295.
29. Yogalingam G, Bonten EJ, van de Vlekkert D, Hu H, Moshiach S, Connell SA et al. Neuraminidase 1 is a negative regulator of lysosomal exocytosis. Dev Cell 2008; 15: 74-86.
30. Cuervo AM, Dice JF. A receptor for the selective uptake and degradation of proteins by lysosomes. Science 1996; 273: 501-503.
31. Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA et al. A gene network regulating lysosomal biogenesis and function. Science 2009; 325: 473-477.
32. Pena-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC, Wolff NC, Tran TA, Zou L et al. Regulation of TFEB and V-ATPases by mTORC1. EMBO J 2011; 30: 3242-3258.
33. Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S et al. TFEB links autophagy to lysosomal biogenesis. Science 2011; 332: 1429-1433.
34. Rawlings ND, Tolle DP, Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res 2004; 32(Database issue): D160-D164.
35. Turk V, Turk B, Turk D. Lysosomal cysteine proteases: facts and opportunities. Embo J 2001; 20: 4629-4633.
36. Gocheva V, Joyce JA. Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 2007; 6: 60-64.
37. Liaudet-Coopman E, Beaujouin M, Derocq D, Garcia M, Glondu-Lassis M, Laurent-Matha V et al. Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett 2006; 237: 167-179.
38. Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene 2008; 27: 6434-6451.
39. Zaidi AU, McDonough JS, Klocke BJ, Latham CB, Korsmeyer SJ, Flavell RA et al. Chloroquine-induced neuronal cell death is p53 and Bcl-2 family-dependent but caspase-independent. J Neuropathol Exp Neurol 2001; 60: 937-945.
40. Reid TR, Torti FM, Ringold GM. Evidence for two mechanisms by which tumor necrosis factor kills cells. J Biol Chem 1989; 264: 4583-4589.
41. Victor BC, Sloane BF. Cysteine cathepsin non-inhibitory binding partners: modulating intracellular trafficking and function. Biol Chem 2007; 388: 1131-1140.
42. Leto G, Tumminello FM, Crescimanno M, Flandina C, Gebbia N. Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. Clin Exp Metastasis 2004; 21: 91-106.
43. Benes P, Vetvicka V, Fusek M. Cathepsin D-many functions of one aspartic protease. Crit Rev Oncol Hematol 2008; 68: 12-28.
44. Benes P, Vashishta A, Saraswat-Ohri S, Fusek M, Pospisilova S, Tichy B et al. Effect of procathepsin D activation peptide on gene expression of breast cancer cells. Cancer Lett 2006; 239: 46-54.
45. Mason SD, Joyce JA. Proteolytic networks in cancer. Trends Cell Biol 2011; 21: 228-237.
46. Jedeszko C, Sloane BF. Cysteine cathepsins in human cancer. Biol Chem 2004; 385: 1017-1027.
47. Yan S, Sloane BF. Molecular regulation of human cathepsin B: implication in pathologies. Biol Chem 2003; 384: 845-854.
48. Kim K, Cai J, Shuja S, Kuo T, Murnane MJ. Presence of activated ras correlates with increased cysteine proteinase activities in human colorectal carcinomas. Int J Cancer 1998; 79: 324-333.
49. Sloane BF, Moin K, Sameni M, Tait LR, Rozhin J, Ziegler G. Membrane association of cathepsin B can be induced by transfection of human breast epithelial cells with c-Ha-ras oncogene. J Cell Sci 1994; 107(Part 2): 373-384.
50. Rafn B, Nielsen CF, Andersen SH, Szyniarowski P, Corcelle-Termeau E, Valo E et al. ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Mol Cell 2012; 45: 764-776.
51. Settembre C, Ballabio A. TFEB regulates autophagy: an integrated coordination of cellular degradation and recycling processes. Autophagy 2011; 7: 1379-1381.
52. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 2006; 20: 543-556.
53. Joyce JA, Hanahan D. Multiple roles for cysteine cathepsins in cancer. Cell Cycle 2004; 3: 1516-1619.
54. Kobayashi H, Schmitt M, Goretzki L, Chucholowski N, Calvete J, Kramer M et al. Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). J Biol Chem 1991; 266: 5147-5152.
55. Mai J, Sameni M, Mikkelsen T, Sloane BF. Degradation of extracellular matrix protein tenascin-C by cathepsin B: an interaction involved in the progression of gliomas. Biol Chem 2002; 383: 1407-1413.
56. Buck MR, Karustis DG, Day NA, Honn KV, Sloane BF. Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochem J 1992; 282(Part 1): 273-278.
57. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 2010; 24: 241-255.
58. Vasiljeva O, Papazoglou A, Kruger A, Brodoefel H, Korovin M, Deussing J et al. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res 2006; 66: 5242-5250.
59. Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Muller S et al. Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene 2011; 30: 54-64.
60. Matarrese P, Ascione B, Ciarlo L, Vona R, Leonetti C, Scarsella M et al. Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study. Mol Cancer 2010; 9: 207.
61. Withana NP, Blum G, Sameni M, Slaney C, Anbalagan A, Olive MB et al. Cathepsin B inhibition limits bone metastasis in breast cancer. Cancer Res 2012; 72: 1199-1209.
62. Ostenfeld MS, Fehrenbacher N, Høyer-Hansen M, Thomsen C, Farkas T, Jäättelä M. Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress. Cancer Res 2005; 65: 8975-8983.
63. Abboud-Jarrous G, Atzmon R, Peretz T, Palermo C, Gadea BB, Joyce JA et al. Cathepsin L is responsible for processing and activation of proheparanase through multiple cleavages of a linker segment. J Biol Chem 2008; 283: 18167-18176.
64. Corvo I, Cancela M, Cappetta M, Pi-Denis N, Tort JF, Roche L. The major cathepsin L secreted by the invasive juvenile Fasciola hepatica prefers proline in the S2 subsite and can cleave collagen. Mol Biochem Parasitol 2009; 167: 41-47.
65. Lankelma JM, Voorend DM, Barwari T, Koetsveld J, Van der Spek AH, De Porto AP et al. Cathepsin L, target in cancer treatment? Life Sci 2010; 86: 225-233.
66. Ishidoh K, Kominami E. Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro. Biochem Biophys Res Commun 1995; 217: 624-631.
67. Strojnik T, Kavalar R, Trinkaus M, Lah TT. Cathepsin L in glioma progression: comparison with cathepsin B. Cancer Detect Prev 2005; 29: 448-455.
68. Rebbaa A, Chu F, Sudha T, Gallati C, Dier U, Dyskin E et al. The anti-angiogenic activity of NSITC, a specific cathepsin L inhibitor. Anticancer Res 2009; 29: 4473-4481.
69. Goulet B, Baruch A, Moon NS, Poirier M, Sansregret LL, Erickson A et al. A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Mol Cell 2004; 14: 207-219.
70. Duncan EM, Muratore-Schroeder TL, Cook RG, Garcia BA, Shabanowitz J, Hunt DF et al. Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation. Cell 2008; 135: 284-294.
71. Ceru S, Konjar S, Maher K, Repnik U, Krizaj I, Bencina M et al. Stefin B interacts with histones and cathepsin L in nucleus. J Biol Chem 2010; 285: 10078-10086.
72. Adams-Cioaba MA, Krupa JC, Xu C, Mort JS, Min J. Structural basis for the recognition and cleavage of histone H3 by cathepsin L. Nat Commun 2011; 2: 197.
73. Sullivan S, Tosetto M, Kevans D, Coss A, Wang L, O'Donoghue D et al. Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer. Int J Cancer 2009; 125: 54-61.
74. Tomoo K. Development of cathepsin inhibitors and structure-based design of cathepsin B-specific inhibitor. Curr Top Med Chem 2010; 10: 696-707.
75. Katunuma N. Structure-based development of specific inhibitors for individual cathepsins and their medical applications. Proc Jpn Acad Ser B Phys Biol Sci 2011; 87: 29-39.
76. Nagaraj NS, Zacharias W. Cigarette smoke condensate increases cathepsin-mediated invasiveness of oral carcinoma cells. Toxicol Lett 2007; 170: 134-145.
77. Katunuma N, Tsuge H, Nukatsuka M, Fukushima M. Structure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis. Adv Enzyme Regul 2002; 42: 159-172.
78. Leto G, Sepporta MV, Crescimanno M, Flandina C, Tumminello FM. Cathepsin L in metastatic bone disease: therapeutic implications. Biol Chem 2010; 391: 655-664.
79. Walz M, Kellermann S, Bylaite M, Andree B, Ruther U, Paus R et al. Expression of the human Cathepsin L inhibitor hurpin in mice: skin alterations and increased carcinogenesis. Exp Dermatol 2007; 16: 715-723.
80. Dennemarker J, Lohmuller T, Mayerle J, Tacke M, Lerch MM, Coussens LM et al. Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis. Oncogene 2010; 29: 1611-1621.
81. Benavides F, Perez C, Blando J, Contreras O, Shen J, Coussens LM et al. Protective role of cathepsin L in mouse skin carcinogenesis. Mol Carcinog (e-pub ahead of print 2 May 2011; doi:10.1002/mc.20792).
82. Boudreau F, Lussier CR, Mongrain S, Darsigny M, Drouin JL, Doyon G et al. Loss of cathepsin L activity promotes claudin-1 overexpression and intestinal neoplasia. FASEB J. 2007; 21: 3853-3865.
83. Reinheckel T, Hagemann S, Dollwet-Mack S, Martinez E, Lohmuller T, Zlatkovic G et al. The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling. J Cell Sci 2005; 118(Part 15): 3387-3395.
84. Grabowskal U, Chambers TJ, Shiroo M. Recent developments in cathepsin K inhibitor design. Curr Opin Drug Discov Devel 2005; 8: 619-630.
85. Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis a lysosomal disease caused by cathepsin K deficiency. Science 1996; 273: 1236-1238.
86. Littlewood-Evans AJ, Bilbe G, Bowler WB, Farley D, Wlodarski B, Kokubo T et al. The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma. Cancer Res 1997; 57: 5386-5390.
87. Le Gall C, Bellahcene A, Bonnelye E, Gasser JA, Castronovo V, Green J et al. A cathepsin K inhibitor reduces breast cancer induced osteolysis and skeletal tumor burden. Cancer Res 2007; 67: 9894-9902.
88. Brubaker KD, Vessella RL, True LD, Thomas R, Corey E, Cathepsin K. mRNA and protein expression in prostate cancer progression. J Bone Miner Res 2003; 18: 222-230.
89. Lewiecki EM. Odanacatib, a cathepsin K inhibitor for the treatment of osteoporosis and other skeletal disorders associated with excessive bone remodeling. IDrugs 2009; 12: 799-809.
90. Quintanilla-Dieck MJ, Codriansky K, Keady M, Bhawan J, Runger TM. Cathepsin K in melanoma invasion. J Invest Dermatol 2008; 128: 2281-2288.
91. Wang B, Sun J, Kitamoto S, Yang M, Grubb A, Chapman HA et al. Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J Biol Chem 2006; 281: 6020-6029.
92. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY et al. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 2004; 5: 443-453.
93. Gocheva V, Chen X, Peters C, Reinheckel T, Joyce JA. Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer. Biol Chem 2010; 391: 937-945.
94. Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Muller S et al. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc Natl Acad Sci USA 2010; 107: 2497-2502.
95. Vasiljeva O, Korovin M, Gajda M, Brodoefel H, Bojic L, Kruger A et al. Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice. Oncogene 2008; 27: 4191-4199.
96. Schurigt U, Sevenich L, Vannier C, Gajda M, Schwinde A, Werner F et al. Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model. Biol Chem 2008; 389: 1067-1074.
97. Li JP. Heparin, heparan sulfate and heparanase in cancer: remedy for metastasis? Anticancer Agents Med Chem 2008; 8: 64-76.
98. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I. A heparin-binding angiogenic protein-basic fibroblast growth factor-is stored within basement membrane. Am J Pathol 1988; 130: 393-400.
99. Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 1999; 68: 729-777.
100. Friedmann Y, Vlodavsky I, Aingorn H, Aviv A, Peretz T, Pecker I et al. Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol 2000; 157: 1167-1175.
101. Shafat I, Ben-Arush MW, Issakov J, Meller I, Naroditsky I, Tortoreto M et al. Pre-clinical and clinical significance of heparanase in Ewing's sarcoma. J Cell Mol Med 2011; 15: 1857-1864.
102. Vlodavsky I, Friedmann Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest 2001; 108: 341-347.
103. Parish CR, Freeman C, Hulett MD. Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta 2001; 1471: M99-108.
104. Shafat I, Vlodavsky I, Ilan N. Characterization of mechanisms involved in secretion of active heparanase. J Biol Chem 2006; 281: 23804-23811.
105. Davidson B, Shafat I, Risberg B, Ilan N, Trope CG, Vlodavsky I et al. Heparanase expression correlates with poor survival in metastatic ovarian carcinoma. Gynecol Oncol 2007; 104: 311-319.
106. Quiros RM, Rao G, Plate J, Harris JE, Brunn GJ, Platt JL et al. Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer 2006; 106: 532-540.
107. Marchetti D, Reiland J, Erwin B, Roy M. Inhibition of heparanase activity and heparanase-induced angiogenesis by suramin analogues. Int J Cancer 2003; 104: 167-174.
108. Vlodavsky I, Mohsen M, Lider O, Svahn CM, Ekre HP, Vigoda M et al. Inhibition of tumor metastasis by heparanase inhibiting species of heparin. Invasion Metastasis 1994; 14: 290-302.
109. Norrby K. Low-molecular-weight heparins and angiogenesis. Apmis, 2006; 114: 79-102.
110. Basche M, Gustafson DL, Holden SN, O'Bryant CL, Gore L, Witta S et al. A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors. Clin Cancer Res 2006; 12: 5471-5480.
111. Liu CJ, Lee PH, Lin DY, Wu CC, Jeng LB, Lin PW et al. Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage. J Hepatol 2009; 50: 958-968.
112. Dredge K, Hammond E, Handley P, Gonda TJ, Smith MT, Vincent C et al. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models. Br J Cancer 2011; 104: 635-642.
113. Bonten E, van der Spoel A, Fornerod M, Grosveld G, d'Azzo A. Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis. Genes Dev 1996; 10: 3156-3169.
114. Miyagi T. Aberrant expression of sialidase and cancer progression. Proc Jpn Acad Ser B Phys Biol Sci 2008; 84: 407-418.
115. Uemura T, Shiozaki K, Yamaguchi K, Miyazaki S, Satomi S, Kato K et al. Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta4. Oncogene 2009; 28: 1218-1229.
116. Saitoh O, Wang WC, Lotan R, Fukuda M. Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem 1992; 267: 5700-5711.
117. Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 2008; 9: 139-150.
118. Saddoughi SA, Song P, Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell Biochem 2008; 49: 413-440.
119. Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogen-esis and treatment. Nat Rev Cancer 2004; 4: 604-616.
120. Linke T, Wilkening G, Lansmann S, Moczall H, Bartelsen O, Weisgerber J et al. Stimulation of acid sphingomyelinase activity by lysosomal lipids and sphingolipid activator proteins. Biol Chem 2001; 382: 283-290.
121. Kornhuber J, Tripal P, Reichel M, Muhle C, Rhein C, Muehlbacher M et al. Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications. Cell Physiol Biochem 2010; 26: 9-20.
122. Carpinteiro A, Dumitru C, Schenck M, Gulbins E. Ceramide-induced cell death in malignant cells. Cancer Lett 2008; 264: 1-10.
123. Dumitru CA, Gulbins E. TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis. Oncogene 2006; 25: 5612-5625.
124. Jenkins RW, Canals D, Hannun YA. Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell Signal 2009; 21: 836-846.
125. Kirkegaard T, Roth AG, Petersen NH, Mahalka AK, Olsen OD, Moilanen I et al. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 2010; 463: 549-553.
126. Heinrich M, Wickel M, Schneider-Brachert W, Sandberg C, Gahr J, Schwandner R et al. Cathepsin D targeted by acid sphingomyelinase-derived ceramide. Embo J 1999; 18: 5252-5263.
127. Canals D, Perry DM, Jenkins RW, Hannun YA. Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases. Br J Pharmacol 2011; 163: 694-712.
128. Hantschel M, Pfister K, Jordan A, Scholz R, Andreesen R, Schmitz G et al. Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress Chaperones 2000; 5: 438-442.
129. Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M et al. Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 2004; 200: 425-435.
130. Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr Drug Targets 2008; 9: 662-673.
131. Ozbayraktar FB, Ulgen KO. Molecular facets of sphingolipids: mediators of diseases. Biotechnol J 2009; 4: 1028-1041.
132. Beckham TH, Lu P, Cheng JC, Zhao D, Turner LS, Zhang X et al. Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B. Int J Cancer (e-pub ahead of print 9 February 2012; doi:10.1002/ijc.27480).
133. Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W. Human acid ceramidase is overexpressed but not mutated in prostate cancer. Genes Chromosomes Cancer 2000; 29: 137-146.
134. Maeda I, Takano T, Matsuzuka F, Maruyama T, Higashiyama T, Liu G et al. Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors. Int J Cancer 1999; 81: 700-704.
135. Ruckhaberle E, Holtrich U, Engels K, Hanker L, Gatje R, Metzler D et al. Acid ceramidase 1 expression correlates with a better prognosis in ER-positive breast cancer. Climacteric 2009; 12: 502-513.
136. Shiraishi N, Akiyama S, Kobayashi M, Kuwano M. Lysosomotropic agents reverse multiple drug resistance in human cancer cells. Cancer Lett 1986; 30: 251-259.
137. Mindell JA. Lysosomal acidification mechanisms. Annu Rev Physiol 2012; 74: 69-86.
138. + signalling in health and disease. Biochem J 2011; 439: 349-374.
139. Otero-Rey EM, Somoza-Martin M, Barros-Angueira F, Garcia-Garcia A. Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene. Oral Oncol 2008; 44: 193-199.
140. Torigoe T, Izumi H, Ishiguchi H, Uramoto H, Murakami T, Ise T et al. Enhanced expression of the human vacuolar H +-ATPase c subunit gene (ATP6L) in response to anticancer agents. J Biol Chem 2002; 277: 36534-36543.
141. Toei M, Saum R, Forgac M. Regulation and isoform function of the V-ATPases. Biochemistry 2010; 49: 4715-4723.
142. Sennoune SR, Bakunts K, Martinez GM, Chua-Tuan JL, Kebir Y, Attaya MN et al. Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity. Am J Physiol Cell Physiol 2004; 286: C1443-C1452.
143. Hinton A, Sennoune SR, Bond S, Fang M, Reuveni M, Sahagian GG et al. Function of a subunit isoforms of the V-ATPase in pH homeostasis and in vitro invasion of MDA-MB231 human breast cancer cells. J Biol Chem 2009; 284: 16400-16408.
144. Nishisho T, Hata K, Nakanishi M, Morita Y, Sun-Wada GH, Wada Y et al. The a3 isoform vacuolar type H-ATPase promotes distant metastasis in the mouse B16 melanoma cells. Mol Cancer Res 9: 845-855.
145. Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Rey JM, Garcia-Garcia A. V-ATPase inhibitors and implication in cancer treatment. Cancer Treat Rev 2009; 35: 707-713.
146. Spugnini EP, Citro G, Fais S. Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy. J Exp Clin Cancer Res 2010; 29: 44.
147. Sugimoto Y, Konoki K, Murata M, Matsushita M, Kanazawa H, Oishi T. Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide. J Med Chem 2009; 52: 798-806.
148. Huss M, Wieczorek H. Inhibitors of V-ATPases: old and new players. J Exp Biol 2009; 212(Part 3): 341-346.
149. Whitehurst AW, Bodemann BO, Cardenas J, Ferguson D, Girard L, Peyton M et al. Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Nature 2007; 446: 815-819.
150. Scaringi L, Cornacchione P, Ayroldi E, Corazzi L, Capodicasa E, Rossi R et al. Omeprazole induces apoptosis in jurkat cells. Int J Immunopathol Pharmacol 2004; 17: 331-342.
151. Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst 2004; 96: 1702-1713.
152. De Milito A, Canese R, Marino ML, Borghi M, Iero M, Villa A et al. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer 2010; 127: 207-219.