AKT inhibitor MK-2206 sensitizes breast cancer cells to MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. PMID: 29313949.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22. PMID: 17993229.
   PubMed Web of Science ®Google Scholar
• Dear RF, McGeechan K, Jenkins MC, et al. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev. 2013 Dec 18;(12):CD008792. PMID: 24347031.
   PubMed Web of Science ®Google Scholar
• Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase iii trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2–negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29(10):1252–1260. PMID: 21383283.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Sun Y. Cullin-RING Ligases as attractive anti-cancer targets. Curr Pharm Des. 2013;19(18):3215–3225. PMID: 23151137.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Morgan MA, Sun Y. Targeting neddylation pathways to inactivate cullin-RING ligases for anticancer therapy. Antioxid Redox Signal. 2014 Dec 10;21(17):2383–2400. PMID: 24410571.
   PubMed Web of Science ®Google Scholar
• Enchev RI, Schulman BA, Peter M. Protein neddylation: beyond cullin-RING ligases. Nat Rev Mol Cell Biol. 2015;16(1):30–44. PMID: 25531226.
   PubMed Web of Science ®Google Scholar
• Brownell JE, Sintchak MD, Gavin JM, et al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol Cell. 2010 Jan 15;37(1):102–111. PMID: 20129059.
   PubMed Web of Science ®Google Scholar
• Zhou L, Zhang W, Sun Y, et al. Protein neddylation and its alterations in human cancers for targeted therapy. Cell Signal. 2018 Apr 1;44:92–102. PMID: 29331584.
   PubMed Web of Science ®Google Scholar
• Yang D, Tan M, Wang G, et al. The p21-dependent radiosensitization of human breast cancer cells by MLN4924, an investigational inhibitor of NEDD8 activating enzyme. Plos One. 2012;7(3):e34079. PMID: 22457814.
   PubMed Web of Science ®Google Scholar
• Oladghaffari M, Shabestani Monfared A, Farajollahi A, et al. MLN4924 and 2DG combined treatment enhances the efficiency of radiotherapy in breast cancer cells. Int J Radiat Biol. 2017 Jun;93(6):590–599. PMID: 28291374.
   PubMed Web of Science ®Google Scholar
• Milhollen Michael A, Thomas Michael P, Narayanan U, et al. Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924. Cancer Cell. 2012;21(3):388–401. PMID: 22439935.
   PubMed Web of Science ®Google Scholar
• Hirai H, Sootome H, Nakatsuru Y, et al. MK-2206, an allosteric AKt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 2010;9(7):1956–1967. PMID: 20571069.
   PubMed Web of Science ®Google Scholar
• Blackburn Jessica S, Liu S, Wilder Jayme L, et al. Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation. Cancer Cell. 2014;25(3):366–378. PMID: 24613413.
   PubMed Web of Science ®Google Scholar
• Will M, Qin ACR, Toy W, et al. Rapid induction of apoptosis by PI3K inhibitors is dependent upon their transient inhibition of RAS–ERK signaling. Cancer Discov. 2014;4(3):334–347. PMID: 24436048.
   PubMed Web of Science ®Google Scholar
• Xiang R-F, Wang Y, Zhang N, et al. MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway. Cell Death Dis. 2017 May 11 online;8:e2776. PMID: 28492559.
   Google Scholar
• Ma CX, Suman V, Goetz MP, et al. A phase II trial of neoadjuvant MK-2206, an AKT inhibitor, with anastrozole in clinical stage II or III PIK3CA-mutant ER-positive and HER2-negative breast cancer. Clin Cancer Res. 2017;23(22):6823–6832. PMID: 28874413.
   PubMed Web of Science ®Google Scholar
• Wisinski KB, Tevaarwerk AJ, Burkard ME, et al. Phase I study of an AKT inhibitor (MK-2206) combined with lapatinib in adult solid tumors followed by dose expansion in advanced HER2+ breast cancer. Clin Cancer Res. 2016;22(11):2659–2667. PMID: 27026198.
   PubMed Web of Science ®Google Scholar
• West KA, Sianna Castillo S, Dennis PA. Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resistance Updat. 2002 Dec 1;5(6):234–248. PMID: 12531180.
   PubMed Web of Science ®Google Scholar
• Koboldt DC, Fulton RSMcLellan MD, et al. Comprehensive molecular portraits of human breast tumours. Nature. 2012 Oct 4;490(7418):61-70. PMID: 23000897.
   Google Scholar
• Knuefermann C, Lu Y, Liu B, et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 2003 May 22 online;22:3205. PMID: 12761490.
   PubMed Web of Science ®Google Scholar
• Qiao M, Sheng S, Pardee AB. Metastasis and AKT activation. Cell Cycle. 2008 Oct 1;7(19):2991–2996. PMID: 18818526.
   PubMed Web of Science ®Google Scholar
• Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747–752. PMID: 10963602.
   PubMed Web of Science ®Google Scholar
• Sorlie T. The impact of gene expression patterns in breast cancer. Clin Chem. 2016 Aug;62(8):1150–1151. PMID: 27022070.
   PubMed Web of Science ®Google Scholar
• Luo M, Fu LW. Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors. Am J Cancer Res. 2014;4(6):608–628. PMID: 25520855.
   PubMed Web of Science ®Google Scholar
• Soucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732–U67. PMID: 19360080.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Xiong X, Jia L, et al. Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell Death Dis. 2012;3:e386. PMID: 22951983.
   PubMed Web of Science ®Google Scholar
• Kane RC, Bross PF, Farrell AT, et al. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist. 2003;8(6):508–513. PMID: 14657528.
   PubMed Web of Science ®Google Scholar
• Orlowski RZ, Kuhn DJ. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res. 2008 March 15 2008;14(6):1649–1657. PMID: 18347166.
   PubMed Web of Science ®Google Scholar
• Fujita T, Doihara H, Washio K, et al. Proteasome inhibitor bortezomib increases PTEN expression and enhances trastuzumab-induced growth inhibition in trastuzumab-resistant cells. Anticancer Drugs. 2006 Apr;17(4):455–462. PMID: 16550004.
   PubMed Web of Science ®Google Scholar
• Yy S, Gw S, Rz O. Proteasome inhibitors induce a p38 Mitogen-activated Protein Kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancer. Breast Cancer Res Treat. 2006 Nov 1;100(1):33–47. PMID: 16807678.
   PubMed Web of Science ®Google Scholar
• Laplante M, Sabatini David M. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–293. PMID: 22500797.
   PubMed Web of Science ®Google Scholar
• Peterson TR, Laplante M, Thoreen CC, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009 May 29;137(5):873–886. PMID: 19446321.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Xiong X, Sun Y. DEPTOR, an mTOR inhibitor, is a physiological substrate of SCFβTrCP E3 ubiquitin ligase and regulates survival and autophagy. Mol Cell. 2011;44(2):304–316. PMID: 22017876.
   PubMed Web of Science ®Google Scholar
• Gao D, Inuzuka H, Tan M-K, et al. mTOR drives its own activation via SCFβTrCP-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell. 2011;44(2):290–303. PMID: 22017875.
   PubMed Web of Science ®Google Scholar
• Duan S, Skaar Jeffrey R, Kuchay S, et al. mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Mol Cell. 2011;44(2):317–324. PMID: 22017877.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Sun Y. Targeting the mTOR-DEPTOR pathway by CRL E3 ubiquitin ligases: therapeutic application. Neoplasia. 2012;14(5):360–367. PMID: 22745582.
   PubMed Web of Science ®Google Scholar
• Zhou X, Tan M, Nyati MK, et al. Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo. Proc Natl Acad Sci U S A. 2016 May 24;113(21):E2935– E2944. PMID: 27162365.
   PubMed Web of Science ®Google Scholar