Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?

Cancer Letters

Volumn 323, Issue 2, 2012, Pages 115-127

  Zhou, Shengtao ^a,b   Zhao, Linjie ^c   Kuang, Manchao ^b   Zhang, Bingjie ^b   Liang, Zhu ^a   Yi, Tao ^a   Wei, Yuquan ^b   Zhao, Xia ^a  

^a SICHUAN UNIVERSITY   (China)

^b SICHUAN UNIVERSITY   (China)

^c CHENGDU UNIVERSITY   (China)

Author keywords

Autophagy; Cancer therapy; Tumorigenesis

Indexed keywords

ARSENIC TRIOXIDE; AUTOPHAGY PROTEIN 5; BCR ABL PROTEIN; BECLIN 1; CISPLATIN; DNA; DOUBLE STRANDED DNA; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; FLUOROURACIL; FULVESTRANT; HISTONE DEACETYLASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IMATINIB; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE LKB1; PROTEIN TYROSINE KINASE; REACTIVE OXYGEN METABOLITE; ROMIDEPSIN; SARACATINIB; SULFORAPHANE; TAMOXIFEN; TEMOZOLOMIDE; THYMIDYLATE SYNTHASE; TRASTUZUMAB; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNINDEXED DRUG; VORINOSTAT;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ATG12 GENE; ATG2B GENE; ATG5 GENE; ATG9B GENE; AUTOPHAGY; B CELL LYMPHOMA; BREAST CANCER; BYSTANDER EFFECT; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CARCINOGENESIS; CELL CYCLE REGULATION; CELL STRESS; CHRONIC MYELOID LEUKEMIA; COLORECTAL CANCER; DNA DAMAGE; DNA STRAND BREAKAGE; DRUG TARGETING; ENDOPLASMIC RETICULUM STRESS; ENZYME INHIBITION; ESOPHAGUS CANCER; FRAMESHIFT MUTATION; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; HUMAN; INHIBITION KINETICS; LEUKEMIA; LIVER CELL CARCINOMA; LUNG ADENOCARCINOMA; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; RHABDOID TUMOR; SHORT SURVEY; SIGNAL TRANSDUCTION; SKIN CANCER; SQUAMOUS CELL CARCINOMA; TUMOR SUPPRESSOR GENE;

EID: 84863098088     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2012.02.017     Document Type: Review

References (142)

1. Xie Z., Klionsky D.J. Autophagosome formation: core machinery and adaptations. Nat. Cell Biol. 2007, 9:1102-1109.
2. Klionsky D.J., Emr S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290:1717-1721.
3. Mijaljica D., Prescott M., Devenish R.J. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 2011, 7:673-682.
4. Li W., Yang Q., Mao Z. Chaperone-mediated autophagy: machinery, regulation and biological consequences. Cell. Mol. Life Sci. 2011, 68:749-763.
5. Mathew R., White E. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr. Opin. Genet. Dev. 2011, 21:113-119.
6. Nishida Y., Arakawa S., Fujitani K., Yamaguchi H., Mizuta T., Kanaseki T., Komatsu M., Otsu K., Tsujimoto Y., Shimizu S. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 2009, 461:U654-U699.
7. Rabinowitz J.D., White E. Autophagy and metabolism. Science 2010, 330:1344-1348.
8. Ogier-Denis E., Codogno P. Autophagy: a barrier or an adaptive response to cancer. Biochim. Biophys. Acta 2003, 1603:113-128.
9. Gozuacik D., Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene 2004, 23:2891-2906.
10. Degenhardt K., Mathew R., Beaudoin B., Bray K., Anderson D., Chen G., Mukherjee C., Shi Y., Gelinas C., Fan Y., Nelson D.A., Jin S., White E. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006, 10:51-64.
11. Kondo Y., Kanzawa T., Sawaya R., Kondo S. The role of autophagy in cancer development and response to therapy. Nat. Rev. Cancer 2005, 5:726-734.
12. Levine B., Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat. Rev. Immunol. 2007, 7:767-777.
13. Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451:1069-1075.
14. Burman C., Ktistakis N.T. Autophagosome formation in mammalian cells. Semin. Immunopathol. 2010, 32:397-413.
15. Liang J., Shao S.H., Xu Z.X., Hennessy B., Ding Z., Larrea M., Kondo S., Dumont D.J., Gutterman J.U., Walker C.L., Slingerland J.M., Mills G.B. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell Biol. 2007, 9:218-224.
16. Ogata M., Hino S., Saito A., Morikawa K., Kondo S., Kanemoto S., Murakami T., Taniguchi M., Tanii I., Yoshinaga K., Shiosaka S., Hammarback J.A., Urano F., Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol. Cell. Biol. 2006, 26:9220-9231.
17. Jung C.H., Ro S.H., Cao J., Otto N.M., Kim D.H. MTOR regulation of autophagy. FEBS Lett. 2010, 584:1287-1295.
18. Pattingre S., Bauvy C., Codogno P. Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells. J. Biol. Chem. 2003, 278:16667-16674.
19. Tsuchihara K., Fujii S., Esumi H. Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues. Cancer Lett. 2009, 278:130-138.
20. Nicholson K.M., Anderson N.G. The protein kinase B/Akt signalling pathway in human malignancy. Cell. Signal. 2002, 14:381-395.
21. Majumder P.K., Sellers W.R. Akt-regulated pathways in prostate cancer. Oncogene 2005, 24:7465-7474.
22. Liu J.J., Lin M., Yu J.Y., Liu B., Bao J.K. Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett. 2011, 300:105-114.
23. Balla T. Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions. J. Cell Sci. 2005, 118:2093-2104.
24. He C., Klionsky D.J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 2009, 43:67-93.
25. Shaw R.J. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol. (Oxf.) 2009, 196:65-80.
26. Shaw R.J., Lamia K.A., Vasquez D., Koo S.H., Bardeesy N., Depinho R.A., Montminy M., Cantley L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005, 310:1642-1646.
27. Nobukuni T., Joaquin M., Roccio M., Dann S.G., Kim S.Y., Gulati P., Byfield M.P., Backer J.M., Natt F., Bos J.L., Zwartkruis F.J., Thomas G. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl. Acad. Sci. USA 2005, 102:14238-14243.
28. Zong W.X., Moll U. P53 in autophagy control. Cell Cycle 2008, 7:2947.
29. Yue Z., Jin S., Yang C., Levine A.J., Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA 2003, 100:15077-15082.
30. Qu X., Yu J., Bhagat G., Furuya N., Hibshoosh H., Troxel A., Rosen J., Eskelinen E.L., Mizushima N., Ohsumi Y., Cattoretti G., Levine B. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 2003, 112:1809-1820.
31. Iqbal J., Kucuk C., Deleeuw R.J., Srivastava G., Tam W., Geng H., Klinkebiel D., Christman J.K., Patel K., Cao K., Shen L., Dybkaer K., Tsui I.F., Ali H., Shimizu N., Au W.Y., Lam W.L., Chan W.C. Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia 2009, 23:1139-1151.
32. Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H., Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999, 402:672-676.
33. Miracco C., Cosci E., Oliveri G., Luzi P., Pacenti L., Monciatti I., Mannucci S., De Nisi M.C., Toscano M., Malagnino V., Falzarano S.M., Pirtoli L., Tosi P. Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours. Int. J. Oncol. 2007, 30:429-436.
34. Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., Jung J.U. Autophagic and tumour suppressor activity of a novel Beclin 1-binding protein UVRAG. Nat. Cell Biol. 2006, 8:688-699.
35. Kim M.S., Jeong E.G., Ahn C.H., Kim S.S., Lee S.H., Yoo N.J. Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. Human Pathol. 2008, 39:1059-1063.
36. Kang M.R., Kim M.S., Oh J.E., Kim Y.R., Song S.Y., Kim S.S., Ahn C.H., Yoo N.J., Lee S.H. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J. Pathol. 2009, 217:702-706.
37. Coppola D., Khalil F., Eschrich S.A., Boulware D., Yeatman T., Wang H.G. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer 2008, 113:2665-2670.
38. Takahashi Y., Coppola D., Matsushita N., Cualing H.D., Sun M., Sato Y., Liang C., Jung J.U., Cheng J.Q., Mule J.J., Pledger W.J., Wang H.G. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat. Cell Biol. 2007, 9:1142-1151.
39. Marino G., Salvador-Montoliu N., Fueyo A., Knecht E., Mizushima N., Lopez-Otin C. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J. Biol. Chem. 2007, 282:18573-18583.
40. Takamura A., Komatsu M., Hara T., Sakamoto A., Kishi C., Waguri S., Eishi Y., Hino O., Tanaka K., Mizushima N. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011, 25:795-800.
41. Mathew R., Kongara S., Beaudoin B., Karp C.M., Bray K., Degenhardt K., Chen G., Jin S., White E. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 2007, 21:1367-1381.
42. Karantza-Wadsworth V., Patel S., Kravchuk O., Chen G., Mathew R., Jin S., White E. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 2007, 21:1621-1635.
43. Mathew R., Karp C.M., Beaudoin B., Vuong N., Chen G., Chen H.Y., Bray K., Reddy A., Bhanot G., Gelinas C., Dipaola R.S., Karantza-Wadsworth V., White E. Autophagy suppresses tumorigenesis through elimination of p62. Cell 2009, 137:1062-1075.
44. Bjorkoy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A., Stenmark H., Johansen T. P62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 2005, 171:603-614.
45. Ahn J.-H., Lee M. Suppression of autophagy sensitizes multidrug resistant cells towards Src tyrosine kinase specific inhibitor PP2. Cancer Lett. 2011, 310:188-197.
46. DeNardo D.G., Johansson M., Coussens L.M. Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 2008, 27:11-18.
47. DeNardo D.G., Barreto J.B., Andreu P., Vasquez L., Tawfik D., Kolhatkar N., Coussens L.M. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 2009, 16:91-102.
48. Bingle L., Brown N.J., Lewis C.E. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J. Pathol. 2002, 196:254-265.
49. Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M., Darot J.F., Tavare S., Arakawa S., Shimizu S., Watt F.M. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009, 23:798-803.
50. Yang S., Wang X., Contino G., Liesa M., Sahin E., Ying H., Bause A., Li Y., Stommel J.M., Dell'Antonio G., Mautner J., Tonon G., Haigis M., Shirihai O.S., Doglioni C., Bardeesy N., Kimmelman A.C. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011, 25 717-729.
51. Lengauer C., Kinzler K.W., Vogelstein B. Genetic instabilities in human cancers. Nature 1998, 396:643-649.
52. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
53. Fung C., Lock R., Gao S., Salas E., Debnath J. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol. Biol. Cell 2008, 19:797-806.
54. Lisanti M.P., Martinez-Outschoorn U.E., Chiavarina B., Pavlides S., Whitaker-Menezes D., Tsirigos A., Witkiewicz A., Lin Z., Balliet R., Howell A., Sotgia F. Understanding the " lethal" drivers of tumor-stroma co-evolution emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol. Ther. 2010, 10:537-542.
55. Kimmelman A.C. The dynamic nature of autophagy in cancer. Genes Dev. 2011, 25:1999-2010.
56. Elgendy M., Sheridan C., Brumatti G., Martin S.J. Oncogenic ras-induced expression of Noxa and Beclin 1 promotes autophagic cell death and limits clonogenic survival. Mol. Cell 2011, 42:23-35.
57. Chen N., Debnath J. Autophagy and tumorigenesis. FEBS Lett. 2010, 584:1427-1435.
58. Loeb L.A., Loeb K.R., Anderson J.P. Multiple mutations and cancer. Proc. Natl. Acad. Sci. USA 2003, 100:776-781.
59. Vivanco I., Sawyers C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2002, 2:489-501.
60. Evan G.I., Vousden K.H. Proliferation, cell cycle and apoptosis in cancer. Nature 2001, 411:342-348.
61. Peltomaki P. Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum. Mol. Genet. 2001, 10:735-740.
62. Levine B., Yuan J. Autophagy in cell death: an innocent convict?. J. Clin. Invest. 2005, 115:2679-2688.
63. Edinger A.L., Thompson C.B. Death by design: apoptosis, necrosis and autophagy. Curr. Opin. Cell Biol. 2004, 16:663-669.
64. Chmiel J.F., Konstan M.W., Knesebeck J.E., Hilliard J.B., Bonfield T.L., Dawson D.V., Berger M. IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice. Am. J. Respir. Crit. Care Med. 1999, 160:2040-2047.
65. Serhan C.N., Jain A., Marleau S., Clish C., Kantarci A., Behbehani B., Colgan S.P., Stahl G.L., Merched A., Petasis N.A., Chan L., Van Dyke T.E. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J. Immunol. 2003, 171:6856-6865.
66. Hengartner M.O. The biochemistry of apoptosis. Nature 2000, 407:770-776.
67. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6:463-477.
68. Lockshin R.A., Zakeri Z. Apoptosis, autophagy, and more. Int. J. Biochem. Cell Biol. 2004, 36:2405-2419.
69. Lee C.Y., Baehrecke E.H. Steroid regulation of autophagic programmed cell death during development. Development 2001, 128:1443-1455.
70. Kosta A., Roisin-Bouffay C., Luciani M.F., Otto G.P., Kessin R.H., Golstein P. Autophagy gene disruption reveals a non-vacuolar cell death pathway in Dictyostelium. J. Biol. Chem. 2004, 279:48404-48409.
71. Xue L., Fletcher G.C., Tolkovsky A.M. Autophagy is activated by apoptotic signalling in sympathetic neurons: an alternative mechanism of death execution. Mol. Cell. Neurosci. 1999, 14:180-198.
72. Xue L., Borutaite V., Tolkovsky A.M. Inhibition of mitochondrial permeability transition and release of cytochrome c by anti-apoptotic nucleoside analogues. Biochem. Pharmacol. 2002, 64:441-449.
73. Yu L., Alva A., Su H., Dutt P., Freundt E., Welsh S., Baehrecke E.H., Lenardo M.J. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 2004, 304:1500-1502.
74. Liu B., Bian H.J., Bao J.K. Plant lectins: potential antineoplastic drugs from bench to clinic. Cancer Lett. 2010, 287:1-12.
75. Maiuri M.C., Zalckvar E., Kimchi A., Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2007, 8:741-752.
76. Mills K.R., Reginato M., Debnath J., Queenan B., Brugge J.S. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro. Proc. Natl. Acad. Sci. USA 2004, 101:3438-3443.
77. Tasdemir E., Maiuri M.C., Galluzzi L., Vitale I., Djavaheri-Mergny M., D'Amelio M., Criollo A., Morselli E., Zhu C., Harper F., Nannmark U., Samara C., Pinton P., Vicencio J.M., Carnuccio R., Moll U.M., Madeo F., Paterlini-Brechot P., Rizzuto R., Szabadkai G., Pierron G., Blomgren K., Tavernarakis N., Codogno P., Cecconi F., Kroemer G. Regulation of autophagy by cytoplasmic p53. Nat. Cell Biol. 2008, 10:676-687.
78. Levine B., Abrams J. P53: the Janus of autophagy?. Nat. Cell Biol. 2008, 10:637-639.
79. Morselli E., Galluzzi L., Kepp O., Vicencio J.M., Criollo A., Maiuri M.C., Kroemer G. Anti- and pro-tumor functions of autophagy. Biochim. Biophys. Acta 2009, 1793:1524-1532.
80. Prins J., Ledgerwood E., Ameloot P., Vandenabeele P., Faraco P., Bright N., O'Rahilly S., Bradley J. Tumour necrosis factor induced autophagy and mitochondrial morphological abnormalities are mediated by TNFR-I and/or TNFR-II and do not invariably lead to cell death. Biochem. Soc. Trans. 1998, 26:S314.
81. Maiuri M.C., Criollo A., Kroemer G. Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. EMBO J. 2010, 29:515-516.
82. Han J., Hou W., Goldstein L.A., Lu C., Stolz D.B., Yin X.M., Rabinowich H. Involvement of protective autophagy in TRAIL resistance of apoptosis-defective tumor cells. J. Biol. Chem. 2008, 283:19665-19677.
83. Thorburn J., Moore F., Rao A., Barclay W.W., Thomas L.R., Grant K.W., Cramer S.D., Thorburn A. Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol. Biol. Cell 2005, 16:1189-1199.
84. Tasdemir E., Chiara Maiuri M., Morselli E., Criollo A., D'Amelio M., Djavaheri-Mergny M., Cecconi F., Tavernarakis N., Kroemer G. A dual role of p53 in the control of autophagy. Autophagy 2008, 4:810-814.
85. Levine B., Sinha S., Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008, 4:600-606.
86. Cheng E.H., Wei M.C., Weiler S., Flavell R.A., Mak T.W., Lindsten T., Korsmeyer S.J. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 2001, 8:705-711.
87. Maiuri M.C., Criollo A., Tasdemir E., Vicencio J.M., Tajeddine N., Hickman J.A., Geneste O., Kroemer G. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy 2007, 3:374-376.
88. Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., Packer M., Schneider M.D., Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005, 122:927-939.
89. Yousefi S., Perozzo R., Schmid I., Ziemiecki A., Schaffner T., Scapozza L., Brunner T., Simon H.U. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 2006, 8:1124-1132.
90. Kanzawa T., Germano I.M., Komata T., Ito H., Kondo Y., Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004, 11:448-457.
91. Schoenlein P.V., Periyasamy-Thandavan S., Samaddar J.S., Jackson W.H., Barrett J.T. Autophagy facilitates the progression of ERalpha-positive breast cancer cells to antiestrogen resistance. Autophagy 2009, 5:400-403.
92. Clarke R., Shajahan A.N., Riggins R.B., Cho Y., Crawford A., Xuan J., Wang Y., Zwart A., Nehra R., Liu M.C. Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells. J. Steroid Biochem. Mol. Biol. 2009, 114:8-20.
93. Vazquez-Martin A., Oliveras-Ferraros C., Menendez J.A. Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab. PLoS ONE 2009, 4:e6251.
94. Milani M., Rzymski T., Mellor H.R., Pike L., Bottini A., Generali D., Harris A.L. The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res. 2009, 69:4415-4423.
95. Fels D.R., Ye J., Segan A.T., Kridel S.J., Spiotto M., Olson M., Koong A.C., Koumenis C. Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathways. Cancer Res. 2008, 68:9323-9330.
96. Bauvy C., Gane P., Arico S., Codogno P., Ogier-Denis E. Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29. Exp. Cell Res. 2001, 268:139-149.
97. Liu D., Yang Y., Liu Q., Wang J. Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells. Med. Oncol. 2011, 28:105-111.
98. Claerhout S., Verschooten L., Van Kelst S., De Vos R., Proby C., Agostinis P., Garmyn M. Concomitant inhibition of AKT and autophagy is required for efficient cisplatin-induced apoptosis of metastatic skin carcinoma. Int. J. Cancer 2010, 127:2790-2803.
99. Abedin M.J., Wang D., McDonnell M.A., Lehmann U., Kelekar A. Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ. 2007, 14:500-510.
100. Ruiz-Irastorza G., Ramos-Casals M., Brito-Zeron P., Khamashta M.A. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann. Rheum. Dis. 2010, 69:20-28.
101. Bellodi C., Lidonnici M.R., Hamilton A., Helgason G.V., Soliera A.R., Ronchetti M., Galavotti S., Young K.W., Selmi T., Yacobi R., Van Etten R.A., Donato N., Hunter A., Dinsdale D., Tirro E., Vigneri P., Nicotera P., Dyer M.J., Holyoake T., Salomoni P., Calabretta B. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J. Clin. Invest. 2009, 119:1109-1123.
102. Gupta A., Roy S., Lazar A.J., Wang W.L., McAuliffe J.C., Reynoso D., McMahon J., Taguchi T., Floris G., Debiec-Rychter M., Schoffski P., Trent J.A., Debnath J., Rubin B.P. Autophagy inhibition and antimalarials promote cell death in gastrointestinal stromal tumor (GIST). Proc. Natl. Acad. Sci. USA 2010, 107:14333-14338.
103. Shingu T., Fujiwara K., Bogler O., Akiyama Y., Moritake K., Shinojima N., Tamada Y., Yokoyama T., Kondo S. Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity in human malignant glioma cells. Int. J. Cancer 2009, 124:1060-1071.
104. Tiwari M., Bajpai V.K., Sahasrabuddhe A.A., Kumar A., Sinha R.A., Behari S., Godbole M.M. Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells. Carcinogenesis 2008, 29:600-609.
105. Wu Z., Chang P.C., Yang J.C., Chu C.Y., Wang L.Y., Chen N.T., Ma A.H., Desai S.J., Lo S.H., Evans C.P., Lam K.S., Kung H.J. Autophagy blockade sensitizes prostate cancer cells towards Src family kinase inhibitors. Genes Cancer 2010, 1:40-49.
106. Vigushin D.M., Coombes R.C. Targeted histone deacetylase inhibition for cancer therapy. Curr. Cancer Drug Targets 2004, 4:205-218.
107. Kanematsu S., Uehara N., Miki H., Yoshizawa K., Kawanaka A., Yuri T., Tsubura A. Autophagy inhibition enhances sulforaphane-induced apoptosis in human breast cancer cells. Anticancer Res. 2010, 30:3381-3390.
108. Carew J.S., Medina E.C., Esquivel J.A., Mahalingam D., Swords R., Kelly K., Zhang H., Huang P., Mita A.C., Mita M.M., Giles F.J., Nawrocki S.T. Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J. Cell Mol. Med. 2010, 14:2448-2459.
109. Watanabe M., Adachi S., Matsubara H., Imai T., Yui Y., Mizushima Y., Hiraumi Y., Watanabe K., Kamitsuji Y., Toyokuni S.Y., Hosoi H., Sugimoto T., Toguchida J., Nakahata T. Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation. Int. J. Cancer 2009, 124:55-67.
110. Shao Y., Gao Z., Marks P.A., Jiang X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA 2004, 101:18030-18035.
111. Carew J.S., Nawrocki S.T., Kahue C.N., Zhang H., Yang C., Chung L., Houghton J.A., Huang P., Giles F.J., Cleveland J.L. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance. Blood 2007, 110:313-322.
112. Longley D.B., Harkin D.P., Johnston P.G. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 2003, 3:330-338.
113. Li J., Hou N., Faried A., Tsutsumi S., Takeuchi T., Kuwano H. Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells. Ann. Surg. Oncol. 2009, 16:761-771.
114. Li J., Hou N., Faried A., Tsutsumi S., Kuwano H. Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model. Eur. J. Cancer 2010, 46:1900-1909.
115. Bijnsdorp I.V., Peters G.J., Temmink O.H., Fukushima M., Kruyt F.A. Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int. J. Cancer 2010, 126:2457-2468.
116. Nguyen T.M., Subramanian I.V., Kelekar A., Ramakrishnan S. Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells. Blood 2007, 109:4793-4802.
117. Gu X., Yao Y., Cheng R., Zhang Y., Dai Z., Wan G., Yang Z., Cai W., Gao G., Yang X. Plasminogen K5 activates mitochondrial apoptosis pathway in endothelial cells by regulating Bak and Bcl-x(L) subcellular distribution. Apoptosis 2011, 16:846-855.
118. Emadi A., Gore S.D. Arsenic trioxide - an old drug rediscovered. Blood Rev. 2010, 24:191-199.
119. Bursch W., Hochegger K., Torok L., Marian B., Ellinger A., Hermann R.S. Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J. Cell Sci. 2000, 113(Pt 7):1189-1198.
120. Okada H., Mak T.W. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 2004, 4:592-603.
121. Qian W., Liu J., Jin J., Ni W., Xu W. Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin 1. Leuk. Res. 2007, 31:329-339.
122. Mathew R., Karantza-Wadsworth V., White E. Role of autophagy in cancer. Nat. Rev. Cancer 2007, 7:961-967.
123. Yousefi S., Simon H.U. Autophagy in cancer and chemotherapy. Results Probl. Cell Differ. 2009, 49:183-190.
124. Dalby K.N., Tekedereli I., Lopez-Berestein G., Ozpolat B. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy 2010, 6:322-329.
125. Shimizu S., Kanaseki T., Mizushima N., Mizuta T., Arakawa-Kobayashi S., Thompson C.B., Tsujimoto Y. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell Biol. 2004, 6:1221-1228.
126. Younes A. Therapeutic activity of mTOR inhibitors in mantle cell lymphoma: clues but no clear answers. Autophagy 2008, 4:707-709.
127. O'Reilly K.E., Rojo F., She Q.B., Solit D., Mills G.B., Smith D., Lane H., Hofmann F., Hicklin D.J., Ludwig D.L., Baselga J., Rosen N. MTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006, 66:1500-1508.
128. Shinohara E.T., Cao C., Niermann K., Mu Y., Zeng F., Hallahan D.E., Lu B. Enhanced radiation damage of tumor vasculature by mTOR inhibitors. Oncogene 2005, 24:5414-5422.
129. Yu K., Shi C., Toral-Barza L., Lucas J., Shor B., Kim J.E., Zhang W.G., Mahoney R., Gaydos C., Tardio L., Kim S.K., Conant R., Curran K., Kaplan J., Verheijen J., Ayral-Kaloustian S., Mansour T.S., Abraham R.T., Zask A., Gibbons J.J. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res. 2010, 70:621-631.
130. Chresta C.M., Davies B.R., Hickson I., Harding T., Cosulich S., Critchlow S.E., Vincent J.P., Ellston R., Jones D., Sini P., James D., Howard Z., Dudley P., Hughes G., Smith L., Maguire S., Hummersone M., Malagu K., Menear K., Jenkins R., Jacobsen M., Smith G.C., Guichard S., Pass M. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010, 70:288-298.
131. Feldman M.E., Apsel B., Uotila A., Loewith R., Knight Z.A., Ruggero D., Shokat K.M. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009, 7:e38.
132. Thoreen C.C., Kang S.A., Chang J.W., Liu Q., Zhang J., Gao Y., Reichling L.J., Sim T., Sabatini D.M., Gray N.S. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 2009, 284:8023-8032.
133. Janes M.R., Limon J.J., So L., Chen J., Lim R.J., Chavez M.A., Vu C., Lilly M.B., Mallya S., Ong S.T., Konopleva M., Martin M.B., Ren P., Liu Y., Rommel C., Fruman D.A. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat. Med. 2010, 16:205-213.
134. Bardeesy N., DePinho R.A. Pancreatic cancer biology and genetics. Nat. Rev. Cancer 2002, 2:897-909.
135. Voss V., Senft C., Lang V., Ronellenfitsch M.W., Steinbach J.P., Seifert V., Kogel D. The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. Mol. Cancer Res. 2010, 8:1002-1016.
136. Lian J., Wu X., He F., Karnak D., Tang W., Meng Y., Xiang D., Ji M., Lawrence T.S., Xu L. A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin 1 interaction at endoplasmic reticulum. Cell Death Differ. 2011, 18:60-71.
137. Akar U., Chaves-Reyez A., Barria M., Tari A., Sanguino A., Kondo Y., Kondo S., Arun B., Lopez-Berestein G., Ozpolat B. Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy 2008, 4:669-679.
138. Akar U., Ozpolat B., Mehta K., Fok J., Kondo Y., Lopez-Berestein G. Tissue transglutaminase inhibits autophagy in pancreatic cancer cells. Mol. Cancer Res. 2007, 5:241-249.
139. Ozpolat B., Akar U., Mehta K., Lopez-Berestein G. PKC delta and tissue transglutaminase are novel inhibitors of autophagy in pancreatic cancer cells. Autophagy 2007, 3:480-483.
140. Hippert M.M., O'Toole P.S., Thorburn A. Autophagy in cancer: good, bad, or both?. Cancer Res. 2006, 66:9349-9351.
141. Shintani T., Klionsky D.J. Autophagy in health and disease: a double-edged sword. Science 2004, 306:990-995.
142. Levy J.M., Thorburn A. Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol. Ther. 2011, 131:130-141.