Disruption of mutated BRAF signaling modulates thyroid cancer phenotype
详细信息 查看全文
- 作者：Elyse K Hanly (1)
Shilpi Rajoria (1)
Zbigniew Darzynkiewicz (2)
Hong Zhao (2)
Robert Suriano (1)
Neha Tuli (1)
Andrea L George (1)
Robert Bednarczyk (1)
Edward J Shin (3)
Jan Geliebter (1)
Raj K Tiwari (1) - 关键词：Thyroid cancer ; BRAFV600E mutation ; PLX4032 ; MAPK signal transduction pathway ; Targeted therapy ; Kinase inhibitors
- 刊名：BMC Research Notes
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：7
- 期：1
- 全文大小：506 KB
- 参考文献：1. Chen AY, Jemal A, Ward EM: Increasing incidence of differentiated thyroid cancer in the United States, 1988-005. / Cancer 2009,115(16):3801-807. CrossRef
2. Davis L, Welch HG: Increasing incidence of thyroid cancer in the United States, 1973-002. / JAMA 2006, 295:2164-167. jama.295.18.2164" target="_blank" title="It opens in new window">CrossRef
3. Aschebrook-Kilfoy B, Schechter RB, Shih YC, Kaplan EL, Chiu BC, Angelos P, Grogan R: The clinical and economic burden of a sustained increase in thyroid cancer incidence. / Cancer Epidemiol Biomarkers Prev 2013. Epub ahead of print
4. Nikiforov YE: Thyroid carcinoma: molecular pathways and therapeutic targets. / Mod Pathol 2008, 21:S37-S43. CrossRef
5. Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D: BRAF mutation in papillary thyroid carcinoma. / J Natl Cancer Inst 2003,95(8):625-27. jnci/95.8.625" target="_blank" title="It opens in new window">CrossRef
6. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA: High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. / Cancer Res 2003, 63:1454.
7. Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R, Sobrinoho-Simoes M: BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. / Oncogene 2003, 22:4578-580. j.onc.1206706" target="_blank" title="It opens in new window">CrossRef
8. Xing M: BRAF mutation in thyroid cancer. / Endocr Relat Cancer 2005,12(2):245-62. CrossRef
9. Riesco-Eizaguirre G, Rodríguez I, De la Vieja A, Costamagna E, Carrasco N, Nistal M, Santisteban P: The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. / Cancer Res 2009,69(21):8317-325. CrossRef
10. Li C, Lee KC, Schneider EB, Zeiger MA: BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. / J Clin Endocrinol Metab 2012,97(12):4559-570. jc.2012-2104" target="_blank" title="It opens in new window">CrossRef
11. Guerra A, Fugazzola L, Marotta V, Cirillo M, Rossi S, Cirello V, Forno I, Moccia T, Budillon A, Vitale M: A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. / Journal Clin Endocrinol Metab 2012,6(7):2333-340. jc.2011-3106" target="_blank" title="It opens in new window">CrossRef
12. Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O’Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, / et al.: Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. / JAMA 2013,309(14):1493-501. jama.2013.3190" target="_blank" title="It opens in new window">CrossRef
13. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehamnn B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA: Roles of the RAF/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. / Biochim Biophys Acta 2007,1773(8):1263-284. j.bbamcr.2006.10.001" target="_blank" title="It opens in new window">CrossRef
14. Garnett MJ, Marais R: Guilty as charged: B-RAF is a human oncogene. / Cancer cell 2004,6(4):313-19. j.ccr.2004.09.022" target="_blank" title="It opens in new window">CrossRef
15. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, / et al.: Mutations of the BRAF gene in human cancer. / Nature 2002, 417:949-54. CrossRef
16. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB: Inhibition of mutated, activated BRAF in metastatic melanoma. / New England Journal of Medicine 2010, 363:809-19. CrossRef
17. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. / N Engl J Med 2011, 364:2507-516. CrossRef
18. Kim K, Cabanillas M, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI: Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring V600E BRAF mutation. / Thyroid 2013. Epub ahead of print
19. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R: Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. / Cell 2004, 116:855-67. CrossRef
20. Polikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N: RAF inhibitors transactivate RAF dimers and ERK signaling in cells with wild-type BRAF. / Nature 2010,464(7287):427-40. CrossRef
21. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B, Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M, Friedman LS, Malek S: Raf inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. / Nature 2010,464(7287):431-35. CrossRef
22. Darzynkiewicz Z, Bedner E, Gorczyca W, Melamed MR: Laser scanning cytometry: a new instrumentation with many applications. / Exp Cell Res 1999, 249:1-2. CrossRef
23. Rajoria S, Suriano R, Shanmugam A, Wilson YL, Schantz SP, Geliebter J, Tiwari RK: Metastatic phenotype is regulated by estrogen in thyroid cells. / Thyroid 2010, 20:33-1. CrossRef
24. Rajoria S, Suriano R, Wilson YL, Schantz SP, Moscatello A, Geliebter J, Tiwari RK: 3,3-Diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways. / Oncol Rep 2011, 25:491-97.
25. Darzynkiewicz Z, Zhao H, Halicka HD, Li J: Cytometry of DNA replication and RNA synthesis: Historical perspective and recent advances based on ‘click chemistry. / Cytometry A 2011, 79A:328-37. CrossRef
26. Bianco R, Melisi D, Ciardiello F, Tortora G: Key cancer cell signal transduction pathways as therapeutic targets. / Eur J Cancer 2006,42(3):290-94. j.ejca.2005.07.034" target="_blank" title="It opens in new window">CrossRef
27. Zhang J, Yang PL, Gray NS: Targeting cancer with small molecule kinase inhibitors. / Nat Rev Cancer 2009, 9:28-9. CrossRef
28. Levitzki A, Klein S: Signal transduction therapy of cancer. / Mol Aspects Med 2010,31(4):287-29. j.mam.2010.04.001" target="_blank" title="It opens in new window">CrossRef
29. Curry JL, Falchook GS, Torres-Cabala C, Tetzlaff MT, Prieto VG: Resistant mechanisms to BRAF inhibitor PLX3032 in melanoma. / Expert Rev Dermatol 2011,6(4):355-57. CrossRef
30. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS: Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. / Nature 2010,468(7326):973-77. CrossRef
31. Salerno P, De Falco V, Tamburrino A, Nappi TC, Vecchio G, Schweppe RE, Bollag G, Santoro M, Salvatore G: Cytostatic activity of adenosine triphosphate-competitive kinase inhibitors in BRAF mutant thyroid carcinoma cells. / J Clin Endocrinol Metab 2010,95(1):450-55. jc.2009-0373" target="_blank" title="It opens in new window">CrossRef
32. Xing J, Liu R, Xing M, Trink B: The BRAF T1799A mutation confers sensitivity of thyroid cancer cells to the BRAF V600E inhibitor PLX4032(RG7204). / Biochem Biophys Res Commun 2011, 28:958-62. j.bbrc.2010.12.088" target="_blank" title="It opens in new window">CrossRef
33. Bollag G, Tsai J, Zhang J, Zhang C, Ibrahim P, Nolop K, Hirth P: Vemurafenib: the first drug approved for BRAF-mutant cancer. / Nat Rev Drug Discov 2012, 11:873-86. CrossRef
34. Sharma SV, Settleman J: Oncogene addiction: setting the stage for molecularly targeted cancer therapy. / Genes Dev 2007,21(24):3214-231. CrossRef
35. Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker JP, Kluger Y, Sznol M: PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. / Pigm Cell Melanoma R 2010, 2:190-00. j.1755-148X.2010.00685.x" target="_blank" title="It opens in new window">CrossRef
36. Liu R, Liu D, Xing M: The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF V600E inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. / J Clin Endocrinol Metab 2012,97(2):E173-E182. jc.2011-1054" target="_blank" title="It opens in new window">CrossRef
37. Montero-Conde C, Ruiz-Llorente S, Dominguez JM, Knauf JA, Viale A, Sherman EJ, Ryder M, Ghossein RA, Rosen N, Fagin JA: Relief of feedback inhibition of HER3 transcription by RAF and MEK inhbitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas. / Cancer Discov 2013,3(5):520-33. CrossRef - 作者单位：Elyse K Hanly (1)
Shilpi Rajoria (1)
Zbigniew Darzynkiewicz (2)
Hong Zhao (2)
Robert Suriano (1)
Neha Tuli (1)
Andrea L George (1)
Robert Bednarczyk (1)
Edward J Shin (3)
Jan Geliebter (1)
Raj K Tiwari (1)
1. Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA
2. Department of Pathology, New York Medical College, Valhalla, New York, 10595, USA
3. Department of Otolaryngology, New York Eye and Ear Infirmary, New York, New York, 10003, USA - ISSN：1756-0500
文摘
Background Thyroid cancer is the most common endocrine-related cancer in the United States and its incidence is rising rapidly. Since among various genetic lesions identified in thyroid cancer, the BRAFV600E mutation is found in 50% of papillary thyroid cancers and 25% of anaplastic thyroid cancers, this mutation provides an opportunity for targeted drug therapy. Our laboratory evaluated cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E-specific inhibitor, in normal BRAF-wild-type thyroid cells and in BRAFV600E-positive papillary thyroid cancer cells. Methods Normal BRAF-wild-type thyroid cells and BRAFV600E-mutated papillary thyroid cancer cells were subjected to proliferation assays and analyzed for cell death by immunofluorescence. Cell cycle status was determined using an EdU uptake assay followed by laser scanning cytometry. In addition, expression of proteins within the MAPK signal transduction pathway was analyzed by Western blot. Results PLX4032 has potent anti-proliferative effects selectively in BRAF-mutated thyroid cancer cells. These effects appear to be mediated by the drug’s activity of inhibiting phosphorylation of signaling molecules downstream of BRAF within the pro-survival MAPK pathway. Interestingly, PLX4032 promotes the phosphorylation of these signaling molecules in BRAF-wild-type thyroid cells. Conclusions These findings support further evaluation of combinational therapy that includes BRAFV600E inhibitors in thyroid cancer patients harboring the BRAFV600E mutation.