MEK1/2 inhibition decreases lactate in BRAF-driven human cancer cells

Cancer Research

Volumn 73, Issue 13, 2013, Pages 4039-4049

  Miniotis, Maria Falck ^a   Arunan, Vaitha ^a   Eykyn, Thomas R ^a,c   Marais, Richard ^b   Workman, Paul ^b   Leach, Martin O ^a   Beloueche Babari, Mounia ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c ST THOMAS HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; B RAF KINASE; CI-1040; GLUCOSE; HEXOKINASE; LACTIC ACID; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; MYC PROTEIN; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; RAS PROTEIN; SELUMETINIB; UNCLASSIFIED DRUG;

ARTICLE; BREAST CANCER; CANCER CELL; CELL METABOLISM; COLORECTAL CANCER; CONTROLLED STUDY; ENZYME INHIBITION; EX VIVO STUDY; GLUCOSE TRANSPORT; GLYCOLYSIS; HEMATOLOGIC MALIGNANCY; HUMAN; HUMAN CELL; IN VITRO STUDY; LACTATE BLOOD LEVEL; MELANOMA; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTEIN DEPLETION;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZAMIDES; BENZIMIDAZOLES; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL PROLIFERATION; DEOXYGLUCOSE; DIPHENYLAMINE; FEMALE; GENE KNOCKDOWN TECHNIQUES; GLUCOSE; HEXOKINASE; HUMANS; LACTIC ACID; MAP KINASE KINASE 1; MAP KINASE KINASE 2; MELANOMA; MICE; MUTATION, MISSENSE; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-MYC; RNA, SMALL INTERFERING; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84880066583     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-1969     Document Type: Article

References (53)

1. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007;26: 3291-310.
2. Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res 2007;13: 1576-83.
3. Hainsworth JD, Cebotaru CL, Kanarev V, Ciuleanu TE, Damyanov D, Stella P, et al. A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J Thorac Oncol 2010;5: 1630-6.
4. Board RE, Ellison G, Orr MC, Kemsley KR, McWalter G, Blockley LY, et al. Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. Br J Cancer 2009;101: 1724-30.
5. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012;367: 107-14.
6. Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439: 358-62.
7. Griffin JL, Shockcor JP. Metabolic profiles of cancer cells. Nat Rev Cancer 2004;4: 551-61.
8. Beloueche-Babari M, Chung YL, Al-Saffar NM, Falck-Miniotis M, Leach MO. Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy. Br J Cancer 2010;102: 1-7.
9. Beloueche-Babari M, Workman P, Leach MO. Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents. Cell Cycle 2011;10: 2883-93.
10. Warburg O. On the origin of cancer cells. Science 1956;123: 309-14.
11. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004;4: 891-9.
12. Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 2008;49: 24S-42S.
13. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 2000;60: 916-21.
14. Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 2004;10: 6661-8.
15. Dafni H, Larson PE, Hu S, Yoshihara HA, Ward CS, Venkatesh HS, et al. Hyperpolarized 13C spectroscopic imaging informs on hypoxiainducible factor-1 and myc activity downstream of platelet-derived growth factor receptor. Cancer Res 2010;70: 7400-10.
16. Ward CS, Venkatesh HS, Chaumeil MM, Brandes AH, Vancriekinge M, Dafni H, et al. Noninvasive detection of target modulation following phosphatidylinositol 3-kinase inhibition using hyperpolarized 13C magnetic resonance spectroscopy. Cancer Res 2010;70: 1296-305.
17. Kole HK, Resnick RJ, Van Doren M, Racker E. Regulation of 6- phosphofructo-1-kinase activity in ras-transformed rat-1 fibroblasts. Arch Biochem Biophys 1991;286: 586-90.
18. Racker E, Resnick RJ, Feldman R. Glycolysis and methylaminoisobutyrate uptake in rat-1 cells transfected with ras or myc oncogenes. Proc Natl Acad Sci U S A 1985;82: 3535-8.
19. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, et al. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 2003;17: 1263-93.
20. Kim JW, Zeller KI, Wang Y, Jegga AG, Aronow BJ, O'Donnell KA, et al. Evaluation ofmyc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Mol Cell Biol 2004;24: 5923-36.
21. Kawauchi K, Araki K, Tobiume K, Tanaka N. p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. Nat Cell Biol 2008;10: 611-8.
22. Wang J, Kobayashi T, Floc'h N, Kinkade CW, Aytes A, Dankort D, et al. B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res 2012;72: 4765-76.
23. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 2009;325: 1555-9.
24. Whittaker S, Ménard D, Kirk R, Ogilvie L, Hedley D, Zambon A, et al. A novel, selective, and efficacious nanomolar pyridopyrazinone inhibitor of V600EBRAF. Cancer Res 2010;70: 8036-44.
25. Beloueche-Babari M, Arunan V, Troy H, Te Poele RH, Wong Te Fong AC, Jackson LE, et al. Histone deacetylase inhibition increases levels of choline kinase alpha and phosphocholine facilitating non-invasive imaging in human cancers. Cancer Res 2012;72: 990-1000.
26. Beloueche-Babari M, Jackson LE, Al-Saffar NM, Eccles SA, Raynaud FI, Workman P, et al. Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3- kinase signaling in human breast cancer cells. Mol Cancer Ther 2006;5: 187-96.
27. Beloueche-Babari M, Jackson LE, Al-Saffar NM, Workman P, Leach MO, Ronen SM. Magnetic resonance spectroscopy monitoring of mitogen-activated protein kinase signaling inhibition. Cancer Res 2005;65: 3356-63.
28. Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, et al. Guidelines for the welfare and use of animals in cancer research. Br J Cancer 2010;102: 1555-77.
29. Ponzio G, Loubat A, Rochet N, Turchi L, Rezzonico R, Farahi Far D, et al. Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction. Oncogene 1998;17: 1159-66.
30. Friday BB, Yu C, Dy GK, Smith PD, Wang L, Thibodeau SN, et al. BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. Cancer Res 2008;68: 6145-53.
31. Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, et al. (V600E) BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci U S A 2009;106: 4519-24.
32. Kerkhoff E, Houben R, Löffler S, Troppmair J, Lee JE, Rapp UR. Regulation of c-myc expression by Ras/Raf signalling. Oncogene 1998;16: 211-6.
33. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363: 809-19.
34. Brower V. BRAF inhibitors: research accelerates in wake of positive findings. J Natl Cancer Inst 2010;102: 214-5.
35. Vizan P, Boros LG, Figueras A, Capella G, Mangues R, Bassilian S, et al. K-ras codon-specific mutations produce distinctive metabolic phenotypes in NIH3T3 mice [corrected] fibroblasts. Cancer Res 2005;65: 5512-5.
36. Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, et al. Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol 2011;7: 523.
37. Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, et al. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A 1997;94: 6658-63.
38. Davies BR, Logie A, McKay JS, Martin P, Steele S, Jenkins R, et al. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther 2007;6: 2209-19.
39. Su JS, Woods SM, Ronen SM. Metabolic consequences of treatment with AKT inhibitor perifosine in breast cancer cells. NMR Biomed 2012;25: 379-88.
40. Dhomen N, Marais R. New insight into BRAF mutations in cancer. Curr Opin Genet Dev 2007;17: 31-9.
41. Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res 2009;69: 565-72.
42. Pascual M, Jahoor F, Reeds PJ. Dietary glucose is extensively recycled in the splanchnic bed of fed adult mice. J Nutr 1997;127: 1480-8.
43. Mathupala SP, Ko YH, Pedersen PL. Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy. Semin Cancer Biol 2009;19: 17-24.
44. Kim JW, Gao P, Liu YC, Semenza GL, Dang CV. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 2007;27: 7381-93.
45. Kim JE, Ahn BC, Hwang MH, Jeon YH, Jeong SY, Lee SW, et al. Combined RNA interference of hexokinase II and (131)I-sodium iodide symporter gene therapy for anaplastic thyroid carcinoma. J Nucl Med 2011;52: 1756-63.
46. Sondergaard JN, Nazarian R, Wang Q, Guo D, Hsueh T, Mok S, et al. Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032. J Transl Med 2010;8: 39.
47. Baudy AR, Dogan T, Flores-Mercado JE, Hoeflich KP, Su F, van Bruggen N, et al. FDG-PET is a good biomarker of both early response and acquired resistance in BRAFV600 mutant melanomas treated with vemurafenib and the MEK inhibitor GDC-0973. EJNMMI Res 2012;2: 22.
48. Lee SC, Poptani H, Pickup S, Jenkins WT, Kim S, Koch CJ, et al. Early detection of radiation therapy response in non-Hodgkin's lymphoma xenografts by in vivo 1H magnetic resonance spectroscopy and imaging. NMR Biomed 2010;23: 624-32.
49. Matsumura A, Isobe T, Takano S, Kawamura H, Anno I. Non-invasive quantification of lactate by proton MR spectroscopy and its clinical applications. Clin Neurol Neurosurg 2005;107: 379-84.
50. Golman K, in 't Zandt R, Thaning M. Real-time metabolic imaging. Proc Natl Acad Sci U S A 2006;103: 11270-5.
51. Day SE, Kettunen MI, Gallagher FA, Hu DE, Lerche M, Wolber J, et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 2007;13: 1382-7.
52. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364: 2507-16.
53. Lee SC, Marzec M, Liu X, Wehrli S, Kantekure K, Ragunath PN, et al. Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma. NMR Biomed 2013;26: 106-14.