Involvement of autophagy in ovarian cancer: A working hypothesis

Journal of Ovarian Research

Volumn 5, Issue 1, 2012, Pages

  Peracchio, Claudia ^a,c   Alabiso, Oscar ^b   Valente, Guido ^c   Isidoro, Ciro ^a,c  

^a Department of Health Sciences   (Italy)

^b Department of Translational Medicine   (Italy)

^c UNIVERSITY OF EASTERN PIEDMONT   (Italy)

Author keywords

Autophagy; Epigenetic; Inflammation; MicroRNA; Ovary cancer

Indexed keywords

AUTOPHAGY PROTEIN 5; BECLIN 1; CARBOPLATIN; HISTONE DEACETYLASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MICRORNA; MICROTUBULE ASSOCIATED PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; TUBACIN; VALPROIC ACID;

APOPTOSIS; AUTOPHAGOSOME; CANCER CELL; CANCER GROWTH; CARCINOGENESIS; CELL DEATH; CELL INFILTRATION; CELL SURVIVAL; CHAPERONE-MEDIATED AUTOPHAGY; DISEASE COURSE; DNA DAMAGE; ENDOSOME; EPIGENETICS; FIBROBLAST; HUMAN; HYPOTHESIS; INFLAMMATION; LYSOSOME; MACROAUTOPHAGY; MACROPHAGE; MICROAUTOPHAGY; MORPHOLOGY; OVARY CANCER; PATHOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STROMA CELL; TUMOR MICROENVIRONMENT; UPREGULATION; VASCULARIZATION;

EID: 84866141632     PISSN: None     EISSN: 17572215     Source Type: Journal    
DOI: 10.1186/1757-2215-5-22     Document Type: Review

References (101)

1. Global cancer statistics. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, CA Cancer J Clin 2011 61 69 90 10.3322/caac.20107 21296855
2. Clinical practice. Screening for ovarian cancer. Clarke-Pearson DL, N Engl J Med 2009 361 170 177 10.1056/NEJMcp0901926 19587342
3. Achievements and unmet needs in the management of advanced ovarian cancer. Guarneri V, Piacentini F, Barbieri E, Conte PF, Gynecol Oncol 2010 117 152 158 10.1016/j.ygyno.2009.11.033 20056266
4. Optimizing molecular-targeted therapies in ovarian cancer: the renewed surge of interest in ovarian cancer biomarkers and cell signaling pathways. Hiss D, J Oncol 2012 2012 737981 22481932
5. Eaten alive: a history of macroautophagy. Yang Z, Klionsky DJ, Nat Cell Biol 2010 12 814 822 10.1038/ncb0910-814 20811353
6. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Itakura E, Mizushima N, Autophagy 2010 6 764 776 10.4161/auto.6.6.12709 20639694
7. Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Mijaljica D, Prescott M, Devenish RJ, Autophagy 2011 7 673 682 10.4161/auto.7.7.14733 21646866
8. Chaperone-mediated autophagy at a glance. Kaushik S, Bandyopadhyay U, Sridhar S, Kiffin R, Martinez-Vicente M, Kon M, Orenstein SJ, Wong E, Cuervo AM, J Cell Sci 2011 124 495 499 10.1242/jcs.073874 21282471
9. Seeing is believing: the impact of electron microscopy on autophagy research. Eskelinen EL, Reggiori F, Baba M, Kovács AL, Seglen PO, Autophagy 2011 7 935 956 10.4161/auto.7.9.15760 21566462
10. Guidelines for the use and interpretation of assays for monitoring autophagy. Klionsky DJ, 1269 others, Autophagy 2012 8 445 544 10.4161/auto.19496 22966490
11. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T, Mol Biol Cell 2008 19 2092 2100 10.1091/mbc.E07-12-1257 18321988
12. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, vervatn A, Bjørkøy G, Johansen T, J Biol Chem 2007 282 24131 24145 10.1074/jbc.M702824200 17580304
13. Autophagy: a lysosomal degradation pathway with a central role in health and disease. Eskelinen EL, Saftig P, Biochim Biophys Acta 2009 1793 664 673 10.1016/j.bbamcr.2008.07.014 18706940
14. Autophagy-lysosomal pathway is involved in lipid degradation in rat liver. Skop V, Cahová M, Papáková Z, Pálení ková E, Daková H, Baranowski M, Zabielski P, Zdychová J, Zídková J, Kazdová L, Physiol Res 2012 61 287 297 22480422
15. Regulation of mammalian autophagy in physiology and pathophysiology. Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M, Luo S, Massey DC, Menzies FM, Moreau K, Narayanan U, Renna M, Siddiqi FH, Underwood BR, Winslow AR, Rubinsztein DC, Physiol Rev 2010 90 1383 1435 10.1152/physrev.00030.2009 20959619
16. Overview of macroautophagy regulation in mammalian cells. Mehrpour M, Esclatine A, Beau I, Codogno P, Cell Res 2010 20 748 762 10.1038/cr.2010.82 20548331
17. Regulation of autophagy by phosphatidylinositol 3-phosphate. Burman C, Ktistakis NT, FEBS Lett 2010 584 1302 1312 10.1016/j.febslet.2010.01.011 20074568
18. mTOR regulation of autophagy. Jung CH, Ro SH, Cao J, Otto NM, Kim DH, FEBS Lett 2010 584 1287 1295 10.1016/j.febslet.2010.01.017 20083114
19. A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29. Ogier-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, Isidoro C, Laburthe M, Codogno P, J Biol Chem 1995 270 13 16 10.1074/jbc.270.1.13 7814364
20. The Beclin 1 interactome. He C, Levine B, Curr Opin Cell Biol 2010 22 140 149 10.1016/j.ceb.2010.01.001 20097051
21. Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P, J Biol Chem 2000 275 992 998 10.1074/jbc.275.2.992 10625637
22. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. Arico S, Petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P, Ogier-Denis E, J Biol Chem 2001 276 35243 35246 10.1074/jbc.C100319200 11477064
23. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL, Proc Natl Acad Sci USA 2010 107 4153 4158 10.1073/pnas.0913860107 20160076
24. Chelation of lisosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells from hydrogen peroxide toxicity by precluding autophagy and Akt dephosphorylation. Castino R, Fiorentino I, Cagnin M, Giovia A, Isidoro C, Toxicol Sci 2011 123 523 541 10.1093/toxsci/kfr179 21742779
25. Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium. Fornai F, Longone P, Ferrucci M, Lenzi P, Isidoro C, Ruggieri S, Paparelli A, Autophagy 2008 4 527 530 18367867
26. Canonical and non-canonical autophagy: variations on a common theme of self-eating? Codogno P, Mehrpour M, Proikas-Cezanne T, Nat Rev Mol Cell Biol 2011 13 7 12 22166994
27. Control of autophagy by oncogenes and tumor suppressor genes. Maiuri MC, Tasdemir E, Criollo A, Morselli E, Vicencio JM, Carnuccio R, Kroemer G, Cell Death Differ 2009 16 87 93 10.1038/cdd.2008.131 18806760
28. Autophagy suppresses tumor progression by limiting chromosomal instability. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, Chen G, Jin S, White E, Genes Dev 2007 21 1367 1381 10.1101/gad.1545107 17510285
29. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B, J Clin Invest 2003 112 1809 1820 14638851
30. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Yue Z, Jin S, Yang C, Levine AJ, Heintz N, Proc Natl Acad Sci USA 2003 100 15077 15082 10.1073/pnas.2436255100 14657337
31. Multi-step process of human breast carcinogenesis: a role for BRCA1, BECN1, CCND1, PTEN and UVRAG. Wu T, Li Y, Gong L, Lu JG, Du XL, Zhang WD, He XL, Wang JQ, Mol Med Report 2012 5 305 312 22011761
32. Autophagy suppresses tumorigenesis through elimination of p62. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, Dipaola RS, Karantza-Wadsworth V, White E, Cell 2009 137 1062 1075 10.1016/j.cell.2009.03.048 19524509
33. Suppression of autophagy by FIP200 deletion impairs DNA damage repair and increases cell death upon treatments with anticancer agents. Bae H, Guan JL, Mol Canc Res 2011 9 1232 1241 10.1158/1541-7786.MCR-11-0098
34. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, Kondo S, Kondo Y, Yu Y, Mills GB, Liao WS, Bast RC Jr, J Clin Invest 2008 118 3917 3929 19033662
35. Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Feng W, Marquez RT, Lu Z, Liu J, Lu KH, Issa JP, Fishman DM, Yu Y, Bast RC Jr, Cancer 2008 112 1489 1502 10.1002/cncr.23323 18286529
36. MicroRNA-modulated autophagic signaling networks in cancer. Fu LL, Wen X, Bao JK, Liu B, Int J Biochem Cell Biol 2012 44 733 736 10.1016/j.biocel.2012. 02.004 22342941
37. Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Zhu H, Wu H, Liu X, Li B, Chen Y, Ren X, Liu CG, Yang JM, Autophagy 2009 5 816 823 19535919
38. miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Korkmaz G, le Sage C, Tekirdag KA, Agami R, Gozuacik D, Autophagy 2012 8 165 176 10.4161/auto.8.2.18351 22248718
39. microRNA-101 is a potent inhibitor of autophagy. Frankel LB, Wen J, Lees M, Høyer-Hansen M, Farkas T, Krogh A, Jäättelä M, Lund AH, EMBO J 2011 30 4628 4641 10.1038/emboj.2011.331 21915098
40. MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1-regulated pathways in mice. Meenhuis A, van Veelen PA, de Looper H, van Boxtel N, van den Berge IJ, Sun SM, Taskesen E, Stern P, de Ru AH, van Adrichem AJ, Demmers J, Jongen-Lavrencic M, Löwenberg B, Touw IP, Sharp PA, Erkeland SJ, Blood 2011 118 916 925 10.1182/blood-2011-02-336487 21628417
41. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, Vouret-Craviari V, Mari B, Barbry P, Mosnier JF, Hébuterne X, Harel-Bellan A, Mograbi B, Darfeuille-Michaud A, Hofman P, Nat Genet 2011 43 242 245 10.1038/ng.762 21278745
42. miR-375 Inhibits Autophagy and Reduces Viability of Hepatocellular Carcinoma Cells Under Hypoxic Conditions. Chang Y, Yan W, He X, Zhang L, Li C, Huang H, Nace G, Geller DA, Lin J, Tsung A, Gastroenterology 2012 143 177 187 e8 10.1053/j.gastro.2012.04.009 22504094
43. microRNA-dependent modulation of histone acetylation in Waldenstrom macroglobulinemia. Roccaro AM, Sacco A, Jia X, Azab AK, Maiso P, Ngo HT, Azab F, Runnels J, Quang P, Ghobrial IM, Blood 2010 116 1506 1514 10.1182/blood-2010- 01-265686 20519629
44. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, Pandey UB, Kaushik S, Tresse E, Lu J, Taylor JP, Cuervo AM, Yao TP, EMBO J 2010 29 969 980 10.1038/emboj.2009.405 20075865
45. Modulation of autophagic activity by extracellular pH. Xu T, Su H, Ganapathy S, Yuan ZM, Autophagy 2011 7 1316 1322 10.4161/auto.7.11.17785 21997366
46. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Hu YL, DeLay M, Jahangiri A, Molinaro AM, Rose SD, Carbonell WS, Aghi MK, Cancer Res 2012 72 7 1773 1783 10.1158/0008-5472.CAN-11-3831 22447568
47. Autophagy and cytokines. Harris J, Cytokine 2011 56 140 144 10.1016/j.cyto.2011.08.022 21889357
48. HIF-1-dependent autophagy protects HeLa cells from fenretinide (4-HPR)-induced apoptosis in hypoxia. Liu XW, Su Y, Zhu H, Cao J, Ding WJ, Zhao YC, He QJ, Yang B, Pharmacol Res 2010 62 416 425 10.1016/j.phrs.2010.07.002 20637870
49. Carcinoma cells activate AMP-activated protein kinase-dependent autophagy as survival response to kaempferol-mediated energetic impairment. Filomeni G, Desideri E, Cardaci S, Graziani I, Piccirillo S, Rotilio G, Ciriolo MR, Autophagy 2010 6 202 216 10.4161/auto.6.2.10971 20083895
50. Mesenchymal stem cells and carcinoma-associated fibroblasts sensitize breast cancer cells in 3D cultures to kinase inhibitors. Dittmer A, Fuchs A, Oerlecke I, Leyh B, Kaiser S, Martens JW, Lützkendorf J, Müller L, Dittmer J, Int J Oncol 2011 39 689 696 21667024
51. Matrix remodeling stimulates stromal autophagy, "fueling" cancer cell mitochondrial metabolism and metastasis. Castello-Cros R, Bonuccelli G, Molchansky A, Capozza F, Witkiewicz AK, Birbe RC, Howell A, Pestell RG, Whitaker-Menezes D, Sotgia F, Lisanti MP, Cell Cycle 2011 10 2021 2034 10.4161/cc.10.12.16002 21646868
52. Leukocyte-cancer cell fusion: initiator of the warburg effect in malignancy? Lazova R, Chakraborty A, Pawelek JM, Adv Exp Med Biol 2011 714 151 172 21506013
53. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Kurman RJ, Shih IM, Am J Surg Pathol 2010 34 433 443 10.1097/PAS.0b013e3181cf3d79 20154587
54. The biology of ovarian cancer: new opportunities for translation. Bast RC Jr, Hennessy B, Mills GB, Nat Rev Cancer 2009 9 415 428 10.1038/nrc2644 19461667
55. Epigenomics of ovarian cancer and its chemoprevention. Chen H, Hardy TM, Tollefsbol TO, Front Genet 2011 2 67 22303362
56. Integrated genomic analyses of ovarian carcinoma. Cancer Genome Atlas Research Network, Nature 2011 474 609 615 10.1038/nature10166 21720365
57. High throughput interrogation of somatic mutations in high grade serous cancer of the ovary. Matulonis UA, Hirsch M, Palescandolo E, Kim E, Liu J, van Hummelen P, MacConaill L, Drapkin R, Hahn WC, PLoS One 2011 6 24433 10.1371/journal.pone.0024433 21931712
58. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Shen Y, Li DD, Wang LL, Deng R, Zhu XF, Autophagy 2008 4 1067 1068 18776739
59. Regulation of autophagy by cytoplasmic p53. Tasdemir E, Maiuri MC, 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 JM, Carnuccio R, Moll UM, Madeo F, Paterlini-Brechot P, Rizzuto R, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G, Nat Cell Biol 2008 10 676 687 10.1038/ncb1730 18454141
60. Transcriptional and posttranscriptional down-regulation of the imprinted tumor suppressor gene ARHI (DRAS3) in ovarian cancer. Lu Z, Luo RZ, Peng H, Rosen DG, Atkinson EN, Warneke C, Huang M, Nishmoto A, Liu J, Liao WS, Yu Y, Bast RC Jr, Clin Cancer Res 2006 12 2404 2413 10.1158/1078-0432.CCR-05-1036 16638845
61. ARHI is a Ras-related small G-protein with a novel N-terminal extension that inhibits growth of ovarian and breast cancers. Luo RZ, Fang X, Marquez R, Liu SY, Mills GB, Liao WS, Yu Y, Bast RC, Oncogene 2003 22 2897 2909 10.1038/sj.onc.1206380 12771940
62. The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways. Badgwell DB, Lu Z, Le K, Gao F, Yang M, Suh GK, Bao JJ, Das P, Andreeff M, Chen W, Yu Y, Ahmed AA, S-L Liao W, Bast RC Jr, Oncogene 2011 31 68 79 21643014
63. Reexpression of the tumor suppressor gene ARHI induces apoptosis in ovarian and breast cancer cells through a caspase-independent calpain-dependent pathway. Bao JJ, Le XF, Wang RY, Yuan J, Wang L, Atkinson EN, LaPushin R, Andreeff M, Fang B, Yu Y, Bast RC Jr, Cancer Res 2002 62 7264 7272 12499268
64. Mammalian target of rapamycin is a biomarker of poor survival in metastatic serous ovarian carcinoma. Bunkholt Elstrand M, Dong HP, degaard E, Holth A, Elloul S, Reich R, Tropé CG, Davidson B, Hum Pathol 2010 41 794 804 10.1016/j.humpath.2009.09.017 20153512
65. Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Nakayama K, Nakayama N, Kurman RJ, Cope L, Pohl G, Samuels Y, Velculescu VE, Wang TL, Shih IM, Canc Biol Ther 2006 5 779 785 10.4161/cbt.5.7.2751
66. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Shoji K, Oda K, Nakagawa S, Hosokawa S, Nagae G, Uehara Y, Sone K, Miyamoto Y, Hiraike H, Hiraike-Wada O, Nei T, Kawana K, Kuramoto H, Aburatani H, Yano T, Taketani Y, Br J Cancer 2009 101 145 148 10.1038/sj.bjc.6605109 19491896
67. PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations. Kolasa IK, Rembiszewska A, Janiec-Jankowska A, Dansonka-Mieszkowska A, Lewandowska AM, Konopka B, Kupryjaczyk J, Gynecol Oncol 2006 103 692 697 10.1016/j.ygyno.2006.05.007 16793127
68. Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma. Davidson B, Hadar R, Schlossberg A, Sternlicht T, Slipicevic A, Skrede M, Risberg B, Flørenes VA, Kopolovic J, Reich R, Hum Pathol 2008 39 87 95 10.1016/j.humpath.2007.05.014 17949781
69. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B, Nature 1999 402 672 676 10.1038/45257 10604474
70. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Crighton D, Wilkinson S, O'Prey J, Syed N, Smith P, Harrison PR, Gasco M, Garrone O, Crook T, Ryan KM, Cell 2006 126 121 134 10.1016/j.cell.2006.05.034 16839881
71. The expression of damage-regulated autophagy modulator 2 (DRAM2) contributes to autophagy induction. Yoon JH, Her S, Kim M, Jang IS, Park J, Mol Biol Rep 2011 39 1087 1093 21584698
72. Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death. Park SM, Kim K, Lee EJ, Kim BK, Lee TJ, Seo T, Jang IS, Lee SH, Kim S, Lee JH, Park J, Biochem Biophys Res Commun 2009 390 1340 1344 10.1016/j.bbrc.2009.10.149 19895784
73. PEA-15 induces autophagy in human ovarian cancer cells and is associated with prolonged overall survival. Bartholomeusz C, Rosen D, Wei C, Kazansky A, Yamasaki F, Takahashi T, Itamochi H, Kondo S, Liu J, Ueno NT, Cancer Res 2008 68 9302 9310 10.1158/0008-5472.CAN-08-2592 19010903
74. The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Kulbe H, Thompson R, Wilson JL, Robinson S, Hagemann T, Fatah R, Gould D, Ayhan A, Balkwill F, Cancer Res 2007 67 585 592 10.1158/0008-5472.CAN-06-2941 17234767
75. Distinct subpopulations of epithelial ovarian cancer cells can differentially induce macrophages and T regulatory cells toward a pro-tumor phenotype. Alvero AB, Montagna MK, Craveiro V, Liu L, Mor G, Am J Reprod Immunol 2012 67 256 265 10.1111/j.1600-0897.2011.01068.x 21917055
76. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. Lane D, Matte I, Rancourt C, Piché A, BMC Canc 2011 11 210 10.1186/1471-2407-11-210
77. Interleukin-6 as a therapeutic target in human ovarian cancer. Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA, Thompson R, Schioppa T, Nemeth J, Vermeulen J, Singh N, Avril N, Cummings J, Rexhepaj E, Jirström K, Gallagher WM, Brennan DJ, McNeish IA, Balkwill FR, Clin Cancer Res 2011 17 6083 6096 10.1158/1078-0432.CCR-11-0945 21795409
78. Up-regulation of interleukin-6 in human ovarian cancer cell via a Gi/PI3K-Akt/NF-kappaB pathway by lysophosphatidic acid, an ovarian cancer-activating factor. Chou CH, Wei LH, Kuo ML, Huang YJ, Lai KP, Chen CA, Hsieh CY, Carcinogenesis 2005 26 45 52 15471896
79. Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. Yu S, Murph MM, Lu Y, Liu S, Hall HS, Liu J, Stephens C, Fang X, Mills GB, J Natl Canc Inst 2008 100 1630 1642 10.1093/jnci/djn378
80. Interleukin-6: A bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells. Delk NA, Farach-Carson MC, Autophagy 2012 8 650 663 10.4161/auto.19226 22441019
81. Lysophosphatidic acid inhibits serum deprivation-induced autophagy in human prostate cancer PC-3 cells. Chang CL, Liao JJ, Huang WP, Lee H, Autophagy 2007 3 268 270 17329959
82. MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy. Boren T, Xiong Y, Hakam A, Wenham R, Apte S, Chan G, Kamath SG, Chen DT, Dressman H, Lancaster JM, Gynecol Oncol 2009 113 249 255 10.1016/j.ygyno.2009.01.014 19237188
83. Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications. Mezzanzanica D, Bagnoli M, De Cecco L, Valeri B, Canevari S, Int J Biochem Cell Biol 2010 42 1262 1272 10.1016/j.biocel.2009.12.017 20035894
84. miRNA profiling along tumour progression in ovarian carcinoma. Vaksman O, Stavnes HT, Kaern J, Trope CG, Davidson B, Reich R, J Cell Mol Med 2011 15 1593 1602 10.1111/j.1582-4934.2010.01148.x 20716115
85. Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumour tissue collections. Marchini S, Cavalieri D, Fruscio R, Calura E, Garavaglia D, Nerini IF, Mangioni C, Cattoretti G, Clivio L, Beltrame L, Katsaros D, Scarampi L, Menato G, Perego P, Chiorino G, Buda A, Romualdi C, D'Incalci M, Lancet Oncol 2011 12 273 285 10.1016/S1470-2045(11)70012-2 21345725
86. MicroRNA-101 Inhibits Growth of Epithelial Ovarian Cancer by Relieving Chromatin-Mediated Transcriptional Repression of p21(waf1/cip1). Semaan A, Qazi AM, Seward S, Chamala S, Bryant CS, Kumar S, Morris R, Steffes CP, Bouwman DL, Munkarah AR, Weaver DW, Gruber SA, Batchu RB, Pharm Res 2011 28 3079 3090 10.1007/s11095-011-0547-x 21818714
87. Targeting CD24 for treatment of ovarian cancer by short hairpin RNA. Su D, Deng H, Zhao X, Zhang X, Chen L, Chen X, Li Z, Bai Y, Wang Y, Zhong Q, Yi T, Qian Z, Wei Y, Cytotherapy 2009 11 642 652 10.1080/14653240902878308 19593703
88. Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway. Zhao Z, Liu XF, Wu HC, Zou SB, Wang JY, Ni PH, Chen XH, Fan QS, Canc Sci 2010 101 1454 1462 10.1111/j.1349-7006.2010.01558.x
89. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ, Cancer Res 2008 68 425 433 10.1158/0008-5472.CAN-07-2488 18199536
90. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Lou Y, Yang X, Wang F, Cui Z, Huang Y, Int J Mol Med 2010 26 819 827 21042775
91. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY, BMC Canc 2006 6 212 10.1186/1471-2407-6-212
92. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M, Sabanay H, Pinkas-Kramarski R, Kimchi A, EMBO Rep 2009 10 285 292 10.1038/embor.2008.246 19180116
93. Targeting the autophagy pathway for cancer chemoprevention. Steeves MA, Dorsey FC, Cleveland JL, Curr Opin Cell Biol 2010 22 218 225 10.1016/j.ceb.2009.12.013 20096553
94. Autophagy as a therapeutic target in cancer. Chen N, Karantza V, Canc Biol Ther 2011 11 157 168 10.4161/cbt.11.2.14622
95. Targeting autophagy during cancer therapy to improve clinical outcomes. Levy JM, Thorburn A, Pharmacol Ther 2011 131 130 141 10.1016/j.pharmthera.2011. 03.009 21440002
96. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, Nelson DA, Jin S, White E, Canc Cell 2006 10 51 64 10.1016/j.ccr.2006.06.001
97. The multiple roles of autophagy in cancer. Rosenfeldt MT, Ryan KM, Carcinogenesis 2011 32 955 963 10.1093/carcin/bgr031 21317301
98. Inhibition of PI3k class III-dependent autophagy prevents apoptosis and necrosis by oxidative stress in dopaminergic neuroblastoma cells. Castino R, Bellio N, Follo C, Murphy D, Isidoro C, Toxicol Sci 2010 117 152 162 10.1093/toxsci/kfq170 20525898
99. Active cell death induced by the anti-estrogens tamoxifen and ICI 164384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Bursch W, Ellinger A, Kienzl H, Török L, Pandey S, Sikorska M, Walker R, Hermann RS, Carcinogenesis 1996 17 1595 1607 10.1093/carcin/17.8.1595 8761415
100. Beyond chemotherapy: targeted therapies in ovarian cancer. Yap TA, Carden CP, Kaye SB, Nat Rev Cancer 2009 9 167 181 10.1038/nrc2583 19238149
101. Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor. Bazzaro M, Lin Z, Santillan A, Lee MK, Wang MC, Chan KC, Bristow RE, Mazitschek R, Bradner J, Roden RB, Clin Cancer Res 2008 14 7340 7347 10.1158/1078-0432.CCR-08-0642 19010849