Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1α and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro

Journal of Cellular Physiology

Volumn 232, Issue 1, 2017, Pages 192-201

  Tanaka, Tomokazu ^a   Ikegami, Yuichi ^a   Nakazawa, Harumasa ^a,b   Kuriyama, Naohide ^a,b   Oki, Miwa ^c   Hanai, Jun Ichi ^c   Sukhatme, Vikas P ^c   Kaneki, Masao ^a,b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b SHRINERS HOSPITALS FOR CHILDREN   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LONAFARNIB; RAS PROTEIN; TIPIFARNIB; TRANSCRIPTION FACTOR SNAIL; UVOMORULIN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL GROWTH; CELL HYPOXIA; CELL METABOLISM; CELL MIGRATION; CELL PROLIFERATION; CELL SELF-RENEWAL; CONTROLLED STUDY; DRUG MECHANISM; HUMAN; HUMAN CELL; IN VITRO STUDY; MCF 7 CELL LINE; MDA MB 231 CELL LINE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRIPLE NEGATIVE BREAST CANCER;

EID: 84987984883     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.25411     Document Type: Article

References (55)

1. Al-Hakeem DA, Fedele S, Carlos R, Porter S. 2007. Extranodal NK/T-cell lymphoma, nasal type. Oral oncol 43:4–14.
2. Andreopoulou E, Vigoda IS, Valero V, Hershman DL, Raptis G, Vahdat LT, Han HS, Wright JJ, Pellegrino CM, Cristofanilli M, Alvarez RH, Fehn K, Fineberg S, Sparano JA. 2013. Phase I-II study of the farnesyl transferase inhibitor tipifarnib plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in HER2/neu-negative inflammatory carcinoma and non-inflammatory estrogen receptor-positive breast carcinoma. Breast Cancer Res Treat 141:429–435.
3. Badve S, Dabbs DJ, Schnitt SJ, Baehner FL, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, Palacios J, Rakha EA, Richardson AL, Schmitt FC, Tan PH, Tse GM, Weigelt B, Ellis IO, Reis-Filho JS. 2011. Basal-like and triple-negative breast cancers: A critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol 24:157–167.
4. Balasis ME, Forinash KD, Chen YA, Fulp WJ, Coppola D, Hamilton AD, Cheng JQ, Sebti SM. 2011. Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice. Clin Cancer Res 17:2852–2862.
5. Bansal N, Petrie K, Christova R, Chung CY, Leibovitch BA, Howell L, Gil V, Sbirkov Y, Lee E, Wexler J, Ariztia EV, Sharma R, Zhu J, Bernstein E, Zhou MM, Zelent A, Farias E, Waxman S. 2015. Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer. Oncotarget 6:34087–34105.
6. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A. 2000. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89.
7. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. 2010. Ketones and lactate “fuel” tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 9:3506–3514.
8. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. 2000. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2:76–83.
9. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM. 2007. The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329–2334.
10. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC. 2006. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502.
11. Cleator S, Heller W, Coombes RC. 2007. Triple-negative breast cancer: Therapeutic options. Lancet 8:235–244.
12. Cohen SJ, Ho L, Ranganathan S, Abbruzzese JL, Alpaugh RK, Beard M, Lewis NL, McLaughlin S, Rogatko A, Perez-Ruixo JJ, Thistle AM, Verhaeghe T, Wang H, Weiner LM, Wright JJ, Hudes GR, Meropol NJ. 2003. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J Clin Oncol 21:1301–1306.
13. Dang H, Ding W, Emerson D, Rountree CB. 2011. Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics. BMC Cancer 11:396.
14. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA. 2007. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434.
15. Eccles SA, Welch DR. 2007. Metastasis: Recent discoveries and novel treatment strategies. Lancet 369:1742–1757.
16. Epling-Burnette PK, Loughran TP, Jr. 2010. Suppression of farnesyltransferase activity in acute myeloid leukemia and myelodysplastic syndrome: Current understanding and recommended use of tipifarnib. Expert Opin Investig Drugs 19:689–698.
17. Esteban MA, Tran MG, Harten SK, Hill P, Castellanos MC, Chandra A, Raval R, O'Brien TS, Maxwell PH. 2006. Regulation of E-cadherin expression by VHL and hypoxia-inducible factor. Cancer Res 66:3567–3575.
18. Figueras A, Arbos MA, Quiles MT, Viñals F, Germà JR, Capellà G. 2013. The impact of KRAS mutations on VEGF-A production and tumour vascular network. BMC Cancer 13:125.
19. Gatenby RA, Gillies RJ. 2004. Why do cancers have high aerobic glycolysis? Nat Rev 4:891–899.
20. Gucalp A, Traina TA. 2011. Triple-negative breast cancer: Adjuvant therapeutic options. Chemother Res Pract 2011:696208.
21. Han D, Wu G, Chang C, Zhu F, Xiao Y, Li Q, Zhang T, Zhang L. 2015. Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway. Oncotarget 6:40907–40919.
22. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144:646–674.
23. Hanai JI, Doro N, Seth P, Sukhatme VP. 2013. ATP citrate lyase knockdown impacts cancer stem cells in vitro. Cell Death Dis 4:e696.
24. Hollestelle A, Elstrodt F, Nagel JH, Kallemeijn WW, Schutte M. 2007. Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines. Mol Cancer Res 5:195–201.
25. Izbicka E, Campos D, Carrizales G, Patnaik A. 2005. Biomarkers of anticancer activity of R115777 (Tipifarnib, Zarnestra) in human breast cancer models in vitro. Anticancer Res 25:3215–3223.
26. Jabbour E, Kantarjian H, Ravandi F, Garcia-Manero G, Estrov Z, Verstovsek S, O'Brien S, Faderl S, Thomas DA, Wright JJ, Cortes J. 2011. A phase 1–2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Cancer 117:1236–1244.
27. Jin H, Eun SY, Lee JS, Park SW, Lee JH, Chang KC, Kim HJ. 2014. P2Y2 receptor activation by nucleotides released from highly metastatic breast cancer cells increases tumor growth and invasion via crosstalk with endothelial cells. Breast Cancer Res 16:R77.
28. Johnston SR, Hickish T, Ellis P, Houston S, Kelland L, Dowsett M, Salter J, Michiels B, Perez-Ruixo JJ, Palmer P, Howes A. 2003. Phase II study of the efficacy and tolerability of two dosing regimens of the farnesyl transferase inhibitor, R115777, in advanced breast cancer. J Clin Oncol 21:2492–2499.
29. Joo YN, Jin H, Eun SY, Park SW, Chang KC, Kim HJ. 2014. P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell MDA-MB-231 contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment. Oncotarget 5:9322–9334.
30. Kamangar F, Dores GM, Anderson WF. 2006. Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150.
31. Kikuchi H, Pino MS, Zeng M, Shirasawa S, Chung DC. 2009. Oncogenic KRAS and BRAF differentially regulate hypoxia-inducible factor-1alpha and -2alpha in colon cancer. Cancer Res 69:8499–8506.
32. Lebowitz PF, Eng-Wong J, Widemann BC, Balis FM, Jayaprakash N, Chow C, Clark G, Gantz SB, Venzon D, Zujewski J. 2005. A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. Clin Cancer Res 11:1247–1252.
33. Lee YJ, Yoon KA, Han JY, Kim HT, Yun T, Lee GK, Kim HY, Lee JS. 2011. Circulating cell-free DNA in plasma of never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. Clin Cancer Res 17:5179–5187.
34. Li T, Guo M, Gradishar WJ, Sparano JA, Perez EA, Wang M, Sledge GW. 2012. A phase II trial of capecitabine in combination with the farnesyltransferase inhibitor tipifarnib in patients with anthracycline-treated and taxane-resistant metastatic breast cancer: An Eastern Cooperative Oncology Group Study (E1103). Breast Cancer Res Treat 134:345–352.
35. Liu M, Sjogren AK, Karlsson C, Ibrahim MX, Andersson KM, Olofsson FJ, Wahlstrom AM, Dalin M, Yu H Chen Z, Yang SH, Young SG, Bergo MO. 2010. Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer. Proc Natl Acad Sci USA 107:6471–6476.
36. Nakazawa H, Yamada M, Tanaka T, Kramer J, Yu YM, Fischman AJ, Martyn JA, Tompkins RG, Kaneki M. 2015. Role of protein farnesylation in burn-induced metabolic derangements and insulin resistance in mouse skeletal muscle. PLoS ONE 10:e0116633.
37. O'Toole SA, Beith JM, Millar EK, West R, McLean A, Cazet A, Swarbrick A, Oakes SR. 2013. Therapeutic targets in triple negative breast cancer. J Clin Pathol 66:530–542.
38. Peto R, Boreham J, Clarke M, Davies C, Beral V. 2000. UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet 355:1822.
39. Rosenberg JE, von der Maase H, Seigne JD, Mardiak J, Vaughn DJ, Moore M, Sahasrabudhe D, Palmer PA, Perez-Ruixo JJ, Small EJ. 2005. A phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with advanced urothelial tract transitional cell carcinoma. Cancer 103:2035–2041.
40. Schwab LP, Peacock DL, Majumdar D, Ingels JF, Jensen LC, Smith KD, Cushing RC, Seagroves TN. 2012. Hypoxia-inducible factor 1alpha promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res 14:R6.
41. Shinozaki S, Chang K, Sakai M, Shimizu N, Yamada M, Tanaka T, Nakazawa H, Ichinose F, Yamada Y, Ishigami A, Ito H, Ouchi Y, Starr ME, Saito H, Shimokado K, Stamler JS, Kaneki M. 2014. Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65. Sci Signal 7:ra106.
42. Siegel R, Naishadham D, Jemal A. 2013. Cancer statistics, 2013. CA Cancer J Clin 63:11–30.
43. Steeg PS, Theodorescu D. 2008. Metastasis: A therapeutic target for cancer. Nat Clin Pract 5:206–219.
44. Stieglitz E, Ward AF, Gerbing RB, Alonzo TA, Arceci RJ, Liu YL, Emanuel PD, Widemann BC, Cheng JW, Jayaprakash N, Balis FM, Castleberry RP, Bunin NJ, Loh ML, Cooper TM. 2015. Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer 62:629–636.
45. Takai E, Tsukimoto M, Harada H, Kojima S. 2014. Autocrine signaling via release of ATP and activation of P2×7 receptor influences motile activity of human lung cancer cells. Purinergic Signal 10:487–497.
46. Tam WL, Weinberg RA. 2013. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med 19:1438–1449.
47. Wang F, Chang M, Shi Y, Jiang L, Zhao J, Hai L, Sharen G, Du H. 2014. Down-regulation of hypoxia-inducible factor-1 suppresses malignant biological behavior of triple-negative breast cancer cells. Int J Clin Exp Med 7:3933–3940.
48. Warnberg F, White D, Anderson E, Knox F, Clarke RB, Morris J, Bundred NJ. 2006. Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo. Breast Cancer Res 8:R21.
49. Wu KL, Huang EY, Jhu EW, Huang YH, Su WH, Chuang PC, Yang KD. 2013. Overexpression of galectin-3 enhances migration of colon cancer cells related to activation of the K-Ras-Raf-Erk1/2 pathway. J Gastroenterol 48:350–359.
50. Xia J, Yu X, Tang L, Li G, He T. 2015. P2×7 receptor stimulates breast cancer cell invasion and migration via the AKT pathway. Oncol Rep 34:103–110.
51. Xiang L, Gilkes DM, Hu H, Takano N, Luo W, Lu H, Bullen JW, Samanta D, Liang H, Semenza GL. 2014. Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype. Oncotarget 5:12509–12527.
52. Xu W, Wang Z, Zhang W, Qian K, Li H, Kong D, Li Y, Tang Y. 2015a. Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/β-catenin signaling pathway. Cancer Lett 356:613–627.
53. Xu X, Tan X, Tampe B, Sanchez E, Zeisberg M, Zeisberg EM. 2015b. Snail is a direct target of hypoxia-inducible factor 1alpha (HIF1alpha) in hypoxia-induced endothelial to mesenchymal transition of human coronary endothelial cells. J Biological Chem 290:16653–16664.
54. Zimmer AS, Steeg PS. 2015. Meaningful prevention of breast cancer metastasis: Candidate therapeutics, preclinical validation, and clinical trial concerns. J Mol Med 93:13–29.
55. Zujewski J, Horak ID, Bol CJ, Woestenborghs R, Bowden C, End DW, Piotrovsky VK, Chiao J, Belly RT, Todd A, Kopp WC, Kohler DR, Chow C, Noone M, Hakim FT, Larkin G, Gress RE, Nussenblatt RB, Kremer AB, Cowan KH. 2000. Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 18:927–941.