Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma

Journal of Clinical Investigation

Volumn 124, Issue 3, 2014, Pages 1406-1417

  Ma, Xiao Hong ^a   Piao, Sheng Fu ^a   Dey, Souvik ^b   McAfee, Quentin ^a   Karakousis, Giorgos ^b   Villanueva, Jessie ^c   Hart, Lori S ^b   Levi, Samuel ^b   Hu, Janice ^a   Zhang, Gao ^c   Lazova, Rossitza ^d   Klump, Vincent ^d   Pawelek, John M ^d   Xu, Xiaowei ^b   Xu, Wei ^a   Schuchter, Lynn M ^a,e   Davies, Michael A ^f   Herlyn, Meenhard ^c   Winkler, Jeffrey ^b,e   Koumenis, Constantinos ^b,e   Amaravadi, Ravi K ^a,e   more..

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c WISTAR INSTITUTE   (United States)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

^f UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 3; ACTIVATING TRANSCRIPTION FACTOR 4; ACTIVATING TRANSCRIPTION FACTOR 6ALPHA; B RAF KINASE; CASPASE 3; CYTOPLASM PROTEIN; DABRAFENIB; GLUCOSE REGULATED PROTEIN 78; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; INITIATION FACTOR 2ALPHA; INOSITOL REQUIRING KINASE 1 ALPHA; LC3 PROTEIN; LC3B PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; N [3 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDINE 3 CARBONYL) 2,4 DIFLUOROPHENYL]PROPANESULFONAMIDE; PROTEIN DISULFIDE ISOMERASE; PROTEIN KINASE R; PROTEIN P62; TRAMETINIB; UNCLASSIFIED DRUG; VEMURAFENIB; X BOX BINDING PROTEIN 1;

ARTICLE; AUTOPHAGY; CELL DEATH; CELL LYSATE; CELL PROTECTION; CELL VIABILITY; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; ENDOPLASMIC RETICULUM STRESS; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; MELANOMA; MELANOMA CELL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR REGRESSION; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; AUTOPHAGY; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; ENDOPLASMIC RETICULUM STRESS; HUMANS; INDOLES; MAP KINASE SIGNALING SYSTEM; MELANOMA; MICE; MICE, NUDE; MUTATION, MISSENSE; PROTO-ONCOGENE PROTEINS B-RAF; SULFONAMIDES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84896757312     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI70454     Document Type: Article

References (52)

1. Flaherty KT, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809-819.
2. Sosman JA, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707-714.
3. Hauschild A, et al. Kaempgen E, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-365.
4. Villanueva J, Vultur A, Herlyn M. Resistance to BRAF inhibitors: unraveling mechanisms and future treatment options. Cancer Res. 2011;71(23):7137-7140.
5. Amaravadi RK, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011;17(4):654-666.
6. Amaravadi RK, Thompson CB. The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Cancer Res. 2007;13(24):7271-7279.
7. Fan QW, et al. Akt and autophagy cooperate to promote survival of drug-resistant glioma. Sci Signal. 2010;3(147):ra81.
8. Amaravadi RK, et al. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 2007;117(2):326-336.
9. Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. Role of autophagy in temozolomideinduced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004;11(4):448-457.
10. Degtyarev M, et al. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol. 2008;183(1):101-116.
11. Rosenfeld MR GS, et al. Pharmacokinetic analysis pharmacodynamic evidence of autophagy inhibition in patients with newly diagnosed glioblastoma treated on a phase I trial of hydroxychloroquine in combination with adjuvant temozolomide radiation (ABTC 0603). J Clin Oncol. 2010; 28(15 suppl):3086.
12. Ma XH, et al. Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma. Clin Cancer Res. 2011;17(10):3478-3489.
13. Lazova R, Klump V, Pawelek J. Autophagy in cutaneous malignant melanoma. J Cutan Pathol. 2010;37(2):256-268.
14. Lazova R, Camp RL, Klump V, Siddiqui SF, Amaravadi RK, Pawelek JM. Punctate LC3B expression is a common feature of solid tumors and associated with proliferation, metastasis, and poor outcome. Clin Cancer Res. 2012;18(2):370-379.
15. Villanueva J, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010;18(6):683-695.
16. Nazarian R, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973-977.
17. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503-2518.
18. Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8(4):445-544.
19. Flaherty KT, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694-1703.
20. McAfee Q, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012;109(21):8253-8258.
21. Zheng B, et al. Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell. 2009;33(2):237-247.
22. Esteve-Puig R, Canals F, Colome N, Merlino G, Recio JA. Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF. PLoS One. 2009;4(3):e4771.
23. Egan DF, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331(6016):456-461.
24. Jung CH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20(7):1992-2003.
25. Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2008;7(12):1013-1030.
26. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059):1081-1086.
27. Jiang HY, et al. Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol Cell Biol. 2004;24(3):1365-1377.
28. Soderberg O, et al. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Meth. 2006;3(12):995-1000.
29. Ni M, Zhang Y, Lee AS. Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. The Biochem J. 2011;434(2):181-188.
30. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000;2(6):326-332.
31. Axten JM, et al. Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl] acetyl}-2,3-dihydro-1Hindol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J Med Chem. 2012;55(16):7193-7207.
32. Deng W, Gopal YN, Scott A, Chen G, Woodman SE, Davies MA. Role and therapeutic potential of PI3K-mTOR signaling in de novo resistance to BRAF inhibition. Pigment Cell Melanoma Res. 2012;25(2):248-258.
33. McArthur GA, et al. Marked, homogeneous and early FDG-PET responses to vemurafenib in BRAF-mutant advanced melanoma. J Clin Oncol. 2012;30(14):1628- 1634.
34. Amaravadi RK, et al. Prolonged responses to vemurafenib in patients with BRAFV600 mutant melanoma with low tumor burden at baseline. Poster presented at: Society for Melanoma Research annual meeting; November 9-13, 2011; Tampa, Florida, USA. Poster #3.
35. Johannessen CM, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468(7326):968-972.
36. Poulikakos PI, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387-390.
37. Abel EV, et al. Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest. 2013;123(5):2155-2168.
38. Haq R, et al. BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proc Natl Acad Sci U S A. 2013;110(11):4321-4326.
39. Haq R, et al. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell. 2013;23(3):302-315.
40. Straussman R, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487(7408):500-504.
41. Bernales S, Schuck S, Walter P. ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy. 2007;3(3):285-287.
42. Yorimitsu T, Nair U, Yang Z, Klionsky DJ. Endoplasmic reticulum stress triggers autophagy. J Biol Chem. 2006;281(40):30299-30304.
43. Kruse KB, Brodsky JL, McCracken AA. Autophagy: an ER protein quality control process. Autophagy. 2006;2(2):135-137.
44. Hart LS, et al. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Invest. 2012;122(12):4621-4634.
45. Rzymski T, et al. Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene. 2010;29(31):4424-4435.
46. Rouschop KM, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest. 2010;120(1):127-141.
47. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30(6):678-688.
48. Beck D, et al. Vemurafenib potently induces endoplasmic reticulum stress-mediated apoptosis in BRAFV600E melanoma cells. Sci Signal. 2013;6(260):ra7.
49. Chapman PB, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-2516.
50. Kamino H, Tam ST. Immunoperoxidase technique modified by counterstain with azure B as a diagnostic aid in evaluating heavily pigmented melanocytic neoplasms. J Cutan Pathol. 1991;18(6):436-439.
51. Lum JJ, DeBerardinis RJ, Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol. 2005;6(6):439-448.
52. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006;1(5):2315-2319.