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Our Science – Neckers Website

Leonard M. Neckers, Ph.D.

Selected Publications

1)  Sourbier C, Scroggins BT, Ratnayake R, Prince TL, Lee S, Lee MJ, Nagy PL, Lee YH, Trepel JB, Beutler JA, Linehan WM, Neckers L.
Englerin A stimulates PKC? to inhibit insulin signaling and to simultaneously activate HSF1: pharmacologically induced synthetic lethality.
Cancer Cell. 23: 228-37, 2013.
2)  Yoshida S, Tsutsumi S, Muhlebach G, Sourbier C, Lee MJ, Lee S, Vartholomaiou E, Tatokoro M, Beebe K, Miyajima N, Mohney RP, Chen Y, Hasumi H, Xu W, Fukushima H, Nakamura K, Koga F, Kihara K, Trepel J, Picard D, Neckers L.
Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis.
Proc. Natl. Acad. Sci. U.S.A. 110: E1604-12, 2013.
3)  Giubellino A, Sourbier C, Lee MJ, Scroggins B, Bullova P, Landau M, Ying W, Neckers L, Trepel JB, Pacak K.
Targeting heat shock protein 90 for the treatment of malignant pheochromocytoma.
PLoS ONE. 8: e56083, 2013.
4)  Miyata Y, Nakamoto H, Neckers L.
The therapeutic target Hsp90 and cancer hallmarks.
Curr. Pharm. Des. 19: 347-65, 2013.
5)  Bourboulia D, Han H, Jensen-Taubman S, Gavil N, Isaac B, Wei B, Neckers L, Stetler-Stevenson WG.
TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.
Oncotarget. 4: 166-76, 2013.
6)  Cheng Q, Chang JT, Geradts J, Neckers LM, Haystead T, Spector NL, Lyerly HK.
Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.
Breast Cancer Res. 14: R62, 2012.
7)  Tsutsumi S, Mollapour M, Prodromou C, Lee CT, Panaretou B, Yoshida S, Mayer MP, Neckers LM.
Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity.
Proc. Natl. Acad. Sci. U.S.A. 109: 2937-42, 2012.
8)  Iwai A, Bourboulia D, Mollapour M, Jensen-Taubman S, Lee S, Donnelly AC, Yoshida S, Miyajima N, Tsutsumi S, Smith AK, Sun D, Wu X, Blagg BS, Trepel JB, Stetler-Stevenson WG, Neckers L.
Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells.
Cell Cycle. 11: 3649-55, 2012.
9)  Xu W, Mollapour M, Prodromou C, Wang S, Scroggins BT, Palchick Z, Beebe K, Siderius M, Lee MJ, Couvillon A, Trepel JB, Miyata Y, Matts R, Neckers L.
Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine.
Mol. Cell. 47: 434-43, 2012.
10)  Solier S, Kohn KW, Scroggins B, Xu W, Trepel J, Neckers L, Pommier Y.
Heat shock protein 90a (HSP90a), a substrate and chaperone of DNA-PK necessary for the apoptotic response.
Proc. Natl. Acad. Sci. U.S.A. 109: 12866-72, 2012.
11)  Neckers L, Workman P.
Hsp90 molecular chaperone inhibitors: are we there yet?.
Clin. Cancer Res. 18: 64-76, 2012.
12)  Kim YS, Kumar V, Lee S, Iwai A, Neckers L, Malhotra SV, Trepel JB.
Methoxychalcone inhibitors of androgen receptor translocation and function.
Bioorg. Med. Chem. Lett. 22: 2105-9, 2012.
13)  Douarre C, Sourbier C, Dalla Rosa I, Brata Das B, Redon CE, Zhang H, Neckers L, Pommier Y.
Mitochondrial topoisomerase I is critical for mitochondrial integrity and cellular energy metabolism.
PLoS ONE. 7: e41094, 2012.
14)  Shim JS, Rao R, Beebe K, Neckers L, Han I, Nahta R, Liu JO.
Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir.
J. Natl. Cancer Inst. 104: 1576-90, 2012.
15)  Xu W, Neckers L.
The double edge of the HSP90-CDC37 chaperone machinery: opposing determinants of kinase stability and activity.
Future Oncol. 8: 939-42, 2012.
16)  Alarcon SV, Mollapour M, Lee MJ, Tsutsumi S, Lee S, Kim YS, Prince T, Apolo AB, Giaccone G, Xu W, Neckers LM, Trepel JB.
Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy.
Curr. Mol. Med. 12: 1125-41, 2012.
17)  Prince T, Neckers L.
A Network of Its Own: The Unique Interactome of the Hsp90 Cochaperone, Sba1/p23.
Mol. Cell. 43: 159-60, 2011.
18)  Matts RL, Brandt GE, Lu Y, Dixit A, Mollapour M, Wang S, Donnelly AC, Neckers L, Verkhivker G, Blagg BS.
A systematic protocol for the characterization of Hsp90 modulators.
Bioorg. Med. Chem. 19: 684-92, 2011.
19)  Moulick K, Ahn JH, Zong H, Rodina A, Cerchietti L, Gomes DaGama EM, Caldas-Lopes E, Beebe K, Perna F, Hatzi K, Vu LP, Zhao X, Zatorska D, Taldone T, Smith-Jones P, Alpaugh M, Gross SS, Pillarsetty N, Ku T, Lewis JS, Larson SM, Levine R, Erdjument-Bromage H, Guzman ML, Nimer SD, Melnick A, Neckers L, Chiosis G.
Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90.
Nat. Chem. Biol. 7: 818-26, 2011.
20)  Mollapour M, Tsutsumi S, Kim YS, Trepel J, Neckers L.
Casein kinase 2 phosphorylation of Hsp90 threonine 22 modulates chaperone function and drug sensitivity.
Oncotarget. 2: 407-17, 2011.
21)  Mollapour M, Neckers L.
Detecting HSP90 phosphorylation.
Methods Mol. Biol. 787: 67-74, 2011.
22)  Koga F, Yoshida S, Tatokoro M, Kawakami S, Fujii Y, Kumagai J, Neckers L, Kihara K.
ErbB2 and NFkappaB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.
PLoS ONE. 6: e27616, 2011.
23)  Yoshida S, Koga F, Tatokoro M, Kawakami S, Fujii Y, Kumagai J, Neckers L, Kihara K.
Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy.
Cell Cycle. 10: 4291-9, 2011.
24)  Mollapour M, Neckers L.
Post-translational modifications of Hsp90 and their contributions to chaperone regulation.
Biochim Biophys Acta. 1823: 648-55, 2011.
25)  Tatokoro M, Koga F, Yoshida S, Kawakami S, Fujii Y, Neckers L, Kihara K.
Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder cancer-initiating cells.
Int J Cancer. 131: 987-96, 2011.
26)  Xu W, Trepel J, Neckers L.
Ras, ROS and proteotoxic stress: a delicate balance.
Cancer Cell. 20: 281-2, 2011.
27)  De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Sang Kim Y, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB.
Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells.
Proc. Natl. Acad. Sci. U.S.A. 108: 11878-83, 2011.
28)  Mollapour M, Tsutsumi S, Truman AW, Xu W, Vaughan CK, Beebe K, Konstantinova A, Vourganti S, Panaretou B, Piper PW, Trepel JB, Prodromou C, Pearl LH, Neckers L.
Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity.
Mol. Cell. 41: 672-81, 2011.
29)  Garcia J, Barluenga S, Beebe K, Neckers L, Winssinger N.
Concise Modular Asymmetric Synthesis of Deguelin, Tephrosin and Investigation into Their Mode of Action.
Chemistry. 16: 9767-71, 2010.
30)  Kong HS, Lee S, Beebe K, Scroggins B, Gupta G, Lee MJ, Jung YJ, Trepel J, Neckers L.
Emetine promotes von Hippel-Lindau-independent degradation of hypoxia-inducible factor-2α in clear cell renal carcinoma.
Mol. Pharmacol. 78: 1072-8, 2010.
31)  Mollapour M, Tsutsumi S, Neckers L.
Hsp90 phosphorylation, Wee1, and the cell cycle.
Cell Cycle. 9: 2310-6, 2010.
32)  Sourbier C, Valera-Romero V, Giubellino A, Yang Y, Sudarshan S, Neckers L, Linehan WM.
Increasing reactive oxygen species as a therapeutic approach to treat hereditary leiomyomatosis and renal cell carcinoma.
Cell Cycle. 9: 4183-9, 2010.
33)  Linehan WM, Bratslavsky G, Pinto PA, Schmidt LS, Neckers L, Bottaro DP, Srinivasan R.
Molecular diagnosis and therapy of kidney cancer.
Annu. Rev. Med. 61: 329-43, 2010.
34)  Kummar S, Gutierrez ME, Gardner ER, Chen X, Figg WD, Zajac-Kaye M, Chen M, Steinberg SM, Muir CA, Yancey MA, Horneffer YR, Juwara L, Melillo G, Ivy SP, Merino M, Neckers L, Steeg PS, Conley BA, Giaccone G, Doroshow JH, Murgo AJ.
Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies.
Eur. J. Cancer. 46: 340-7, 2010.
35)  Mollapour M, Neckers L.
Quinacrine: New anti-tumor application for an old anti-malaria drug.
Cell Cycle. 9: 228, 2010.
36)  Wang Y, Trepel JB, Neckers LM, Giaccone G.
STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer.
Curr Opin Investig Drugs. 11: 1466-76, 2010.
37)  Mollapour M, Tsutsumi S, Donnelly AC, Beebe K, Tokita MJ, Lee MJ, Lee S, Morra G, Bourboulia D, Scroggins BT, Colombo G, Blagg BS, Panaretou B, Stetler-Stevenson WG, Trepel JB, Piper PW, Prodromou C, Pearl LH, Neckers L.
Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function.
Mol. Cell. 37: 333-43, 2010.
38)  Trepel J, Mollapour M, Giaccone G, Neckers L.
Targeting the dynamic HSP90 complex in cancer.
Nat. Rev. Cancer. 10: 537-49, 2010.
39)  Vaughan CK, Neckers L, Piper PW.
Understanding of the Hsp90 molecular chaperone reaches new heights.
Nat. Struct. Mol. Biol. 17: 1400-4, 2010.
40)  Yang Y, Valera VA, Padilla-Nash HM, Sourbier C, Vocke CD, Vira MA, Abu-Asab MS, Bratslavsky G, Tsokos M, Merino MJ, Pinto PA, Srinivasan R, Ried T, Neckers L, Linehan WM.
UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer.
Cancer Genet. Cytogenet. 196: 45-55, 2010.
41)  Wang S, Pashtan I, Tsutsumi S, Xu W, Neckers L.
Cancer cells harboring MET gene amplification activate alternative signaling pathways to escape MET inhibition but remain sensitive to Hsp90 inhibitors.
Cell Cycle. 8: 2050-6, 2009.
42)  Kang BH, Plescia J, Song HY, Meli M, Colombo G, Beebe K, Scroggins B, Neckers L, Altieri DC.
Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90.
J. Clin. Invest. 119: 454-64, 2009.
43)  Sudarshan S, Sourbier C, Kong H, Block K, Romero VV, Yang Y, Galindo C, Mollapour M, Scroggins B, Goode N, Lee M, Gourlay CW, Trepel J, Linehan WM, Neckers L.
Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and HIF-1{alpha} stabilization by glucose-dependent generation of reactive oxygen species.
Mol. Cell. Biol. 29: 4080-90, 2009.
44)  Kawabe M, Mandic M, Taylor JL, Vasquez CA, Wesa AK, Neckers LM, Storkus WJ.
Heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhances EphA2+ tumor cell recognition by specific CD8+ T cells.
Cancer Res. 69: 6995-7003, 2009.
45)  Linehan WM, Pinto PA, Bratslavsky G, Pfaffenroth E, Merino M, Vocke CD, Toro JR, Bottaro D, Neckers L, Schmidt LS, Srinivasan R.
Hereditary kidney cancer: unique opportunity for disease-based therapy.
Cancer. 115: 2252-61, 2009.
46)  Tsutsumi S, Mollapour M, Graf C, Lee CT, Scroggins BT, Xu W, Haslerova L, Hessling M, Konstantinova AA, Trepel JB, Panaretou B, Buchner J, Mayer MP, Prodromou C, Neckers L.
Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain.
Nat. Struct. Mol. Biol. 16: 1141-7, 2009.
47)  Tsutsumi S, Beebe K, Neckers L.
Impact of heat-shock protein 90 on cancer metastasis.
Future Oncol. 5: 679-88, 2009.
48)  Koga F, Kihara K, Neckers L.
Inhibition of cancer invasion and metastasis by targeting the molecular chaperone heat-shock protein 90.
Anticancer Res. 29: 797-807, 2009.
49)  Barluenga S, Fontaine JG, Wang C, Aouadi K, Chen R, Beebe K, Neckers L, Winssinger N.
Inhibition of HSP90 with pochoximes: SAR and structure-based insights.
Chembiochem. 10: 2753-9, 2009.
50)  Scroggins BT, Neckers L.
Just say NO: nitric oxide regulation of Hsp90.
EMBO Rep. 10: 1093-4, 2009.
51)  Ehrlich ES, Wang T, Luo K, Xiao Z, Niewiadomska AM, Martinez T, Xu W, Neckers L, Yu XF.
Regulation of Hsp90 client proteins by a Cullin5-RING E3 ubiquitin ligase.
Proc. Natl. Acad. Sci. U.S.A. 106: 20330-5, 2009.
52)  Neckers L, Mollapour M, Tsutsumi S.
The complex dance of the molecular chaperone Hsp90.
Trends Biochem. Sci. 34: 223-6, 2009.
53)  Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, Neckers L, Trepel JB.
Update on Hsp90 inhibitors in clinical trial.
Curr Top Med Chem. 9: 1479-92, 2009.
54)  Neckers L, Tsutsumi S, Mollapour M.
Visualizing the twists and turns of a molecular chaperone.
Nat. Struct. Mol. Biol. 16: 235-6, 2009.
55)  Tsutsumi S, Scroggins B, Koga F, Lee MJ, Trepel J, Felts S, Carreras C, Neckers L.
A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasion.
Oncogene. 27: 2478-87, 2008.
56)  Asami Y, Kakeya H, Komi Y, Kojima S, Nishikawa K, Beebe K, Neckers L, Osada H.
Azaspirene, a fungal product, inhibits angiogenesis by blocking Raf-1 activation.
Cancer Sci. 99: 1853-8, 2008.
57)  Barluenga S, Wang C, Fontaine JG, Aouadi K, Beebe K, Tsutsumi S, Neckers L, Winssinger N.
Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor.
Angew. Chem. Int. Ed. Engl. 47: 4432-5, 2008.
58)  Vaughan CK, Mollapour M, Smith JR, Truman A, Hu B, Good VM, Panaretou B, Neckers L, Clarke PA, Workman P, Piper PW, Prodromou C, Pearl LH.
Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37.
Mol. Cell. 31: 886-95, 2008.
59)  Yano A, Tsutsumi S, Soga S, Lee MJ, Trepel J, Osada H, Neckers L.
Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone.
Proc. Natl. Acad. Sci. U.S.A. 105: 15541-6, 2008.
60)  Gallegos Ruiz MI, Floor K, Roepman P, Rodriguez JA, Meijer GA, Mooi WJ, Jassem E, Niklinski J, Muley T, van Zandwijk N, Smit EF, Beebe K, Neckers L, Ylstra B, Giaccone G.
Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
PLoS ONE. 3: e0001722, 2008.
61)  Kajiguchi T, Lee S, Lee MJ, Trepel JB, Neckers L.
KIT regulates tyrosine phosphorylation and nuclear localization of beta-catenin in mast cell leukemia.
Leuk. Res. 32: 761-70, 2008.
62)  Park Y, Kubo A, Komiya T, Coxon A, Beebe K, Neckers L, Meltzer PS, Kaye FJ.
Low-penetrant RB allele in small-cell cancer shows geldanamycin instability and discordant expression with mutant ras.
Cell Cycle. 7: 2384-91, 2008.
63)  Neckers L, Tatu U.
Molecular chaperones in pathogen virulence: emerging new targets for therapy.
Cell Host Microbe. 4: 519-27, 2008.
64)  Pashtan I, Tsutsumi S, Wang S, Xu W, Neckers L.
Targeting Hsp90 prevents escape of breast cancer cells from tyrosine kinase inhibition.
Cell Cycle. 7: 2936-41, 2008.
65)  Lev A, Takeda K, Zanker D, Maynard JC, Dimberu P, Waffarn E, Gibbs J, Netzer N, Princiotta MF, Neckers L, Picard D, Nicchitta CV, Chen W, Reiter Y, Bennink JR, Yewdell JW.
The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation.
Immunity. 28: 787-98, 2008.
66)  Ansar S, Burlison JA, Hadden MK, Yu XM, Desino KE, Bean J, Neckers L, Audus KL, Michaelis ML, Blagg BS.
A non-toxic Hsp90 inhibitor protects neurons from Abeta-induced toxicity.
Bioorg. Med. Chem. Lett. 17: 1984-90, 2007.
67)  Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K, Cotter RJ, Felts S, Toft D, Karnitz L, Rosen N, Neckers L.
An acetylation site in the middle domain of Hsp90 regulates chaperone function.
Mol. Cell. 25: 151-9, 2007.
68)  Jung Y, Xu W, Kim H, Ha N, Neckers L.
Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin.
Biochim. Biophys. Acta. 1773: 383-90, 2007.
69)  Workman P, Burrows F, Neckers L, Rosen N.
Drugging the cancer chaperone HSP90: Combinatorial therapeutic exploitation of oncogene addiction and tumor stress.
Ann N Y Acad Sci. 1113: 202-16, 2007.
70)  Tsutsumi S, Neckers L.
Extracellular heat shock protein 90: A role for a molecular chaperone in cell motility and cancer metastasis.
Cancer Sci. 98: 1536-9, 2007.
71)  Kajiguchi T, Chung EJ, Lee S, Stine A, Kiyoi H, Naoe T, Levis MJ, Neckers L, Trepel JB.
FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells.
Leukemia. 21: 2476-84, 2007.
72)  Neckers L.
Heat shock protein 90: the cancer chaperone.
J. Biosci. 32: 517-30, 2007.
73)  Sudarshan S, Linehan WM, Neckers L.
HIF and fumarate hydratase in renal cancer.
Br. J. Cancer. 96: 403-7, 2007.
74)  Neckers L, Kern A, Tsutsumi S.
Hsp90 inhibitors disrupt mitochondrial homeostasis in cancer cells.
Chem. Biol. 14: 1204-6, 2007.
75)  Linehan WM, Pinto PA, Srinivasan R, Merino M, Choyke P, Choyke L, Coleman J, Toro J, Glenn G, Vocke C, Zbar B, Schmidt LS, Bottaro D, Neckers L.
Identification of the genes for kidney cancer: opportunity for disease-specific targeted therapeutics.
Clin. Cancer Res. 13: 671s-679s, 2007.
76)  Williams CR, Tabios R, Linehan WM, Neckers L.
Intratumor Injection of the Hsp90 Inhibitor 17AAG Decreases Tumor Growth and Induces Apoptosis in a Prostate Cancer Xenograft Model.
J. Urol. 178: 1528-32, 2007.
77)  Xu W, Yuan X, Beebe K, Xiang Z, Neckers L.
Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity.
Mol. Cell. Biol. 27: 220-8, 2007.
78)  Koga F, Tsutsumi S, Neckers LM.
Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells.
Cell Cycle. 6: 1393-402, 2007.
79)  Sudarshan S, Pinto PA, Neckers L, Linehan WM.
Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer.
Nat Clin Pract Urol. 4: 104-10, 2007.
80)  Bratslavsky G, Sudarshan S, Neckers L, Linehan WM.
Pseudohypoxic pathways in renal cell carcinoma.
Clin. Cancer Res. 13: 4667-71, 2007.
81)  Xu W, Soga S, Beebe K, Lee MJ, Kim YS, Trepel J, Neckers L.
Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition.
Br. J. Cancer. 97: 741-4, 2007.
82)  Xu W, Neckers L.
Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells.
Clin. Cancer Res. 13: 1625-9, 2007.
83)  Kim H, Jeon H, Kong H, Yang Y, Choi B, Kim YM, Neckers L, Jung Y.
A molecular mechanism for the anti-inflammatory effect of taurine-conjugated 5-aminosalicylic acid in inflamed colon.
Mol. Pharmacol. 69: 1405-12, 2006.
84)  Neckers L.
Chaperoning oncogenes: Hsp90 as a target of geldanamycin.
Handb Exp Pharmacol. 172: 259-77, 2006.
85)  Marcu MG, Jung Y, Lee S, Chung E, Lee M, Trepel J, Neckers L.
Curcumin is an inhibitor of p300 histone acetylatransferase.
Med Chem. 2: 169-74, 2006.
86)  Mimnaugh EG, Xu W, Vos M, Yuan X, Neckers L.
Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade.
Mol. Cancer Res. 4: 667-81, 2006.
87)  Koga F, Xu W, Karpova TS, McNally JG, Baron R, Neckers L.
Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation.
Proc. Natl. Acad. Sci. U.S.A. 103: 11318-22, 2006.
88)  Lattouf J, Srinivasan R, Pinto PA, Linehan WM, Neckers L.
Mechanisms of disease: the role of heat-shock protein 90 in genitourinary malignancy.
Nat Clin Pract Urol. 3: 590-601, 2006.
89)  Burlison JA, Neckers L, Smith AB, Maxwell A, Blagg BS.
Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90.
J. Am. Chem. Soc. 128: 15529-36, 2006.
90)  Chiosis G, Neckers L.
Tumor selectivity of Hsp90 inhibitors: the explanation remains elusive.
ACS Chem. Biol. 1: 279-84, 2006.
91)  Yang Q, Kim YS, Lin Y, Lewis J, Neckers L, Liu ZG.
Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK.
EMBO Rep. 7: 622-7, 2006.
92)  Neckers L.
Using natural product inhibitors to validate hsp90 as a molecular target in cancer.
Curr Top Med Chem. 6: 1163-71, 2006.
93)  Gotlib J, Berubé C, Growney JD, Chen C, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutré SE.
Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation.
Blood. 106: 2865-70, 2005.
94)  Wang D, Xu W, McGrath SC, Patterson C, Neckers L, Cotter RJ.
Direct identification of ubiquitination sites on ubiquitin-conjugated CHIP using MALDI mass spectrometry.
J. Proteome Res. 4: 1554-60, 2005.
95)  Neckers L, Neckers K.
Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics - an update.
Expert Opin Emerg Drugs. 10: 137-49, 2005.
96)  Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, Merino M, Trepel J, Zbar B, Toro J, Ratcliffe PJ, Linehan WM, Neckers L.
HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability.
Cancer Cell. 8: 143-53, 2005.
97)  Yu XM, Shen G, Neckers L, Blake H, Holzbeierlein J, Cronk B, Blagg BS.
Hsp90 inhibitors identified from a library of novobiocin analogues.
J. Am. Chem. Soc. 127: 12778-9, 2005.
98)  Mimnaugh EG, Neckers LM.
Measuring ubiquitin conjugation in cells.
Methods Mol. Biol. 301: 223-41, 2005.
99)  Kim H, Kong H, Choi B, Yang Y, Kim Y, Lim MJ, Neckers L, Jung Y.
Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease.
Pharm. Res. 22: 1499-509, 2005.
100)  Wei M, Toure O, Glenn GM, Pithukpakorn M, Neckers L, Stolle C, Choyke P, Grubb R, Middelton L, Turner ML, Walther MM, Merino MJ, Zbar B, Linehan WM, Toro JR.
Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.
J Med Genet. 43: 18-27, 2005.
101)  Grem JL, Morrison G, Guo XD, Agnew E, Takimoto CH, Thomas R, Szabo E, Grochow L, Grollman F, Hamilton JM, Neckers L, Wilson RH.
Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors.
J Clin Oncol. 23: 1885-93, 2005.
102)  Xu W, Yuan X, Xiang Z, Mimnaugh E, Marcu M, Neckers L.
Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex.
Nat Struct Mol Biol. 12: 120-6, 2005.
103)  Fumo G, Akin C, Metcalfe DD, Neckers L.
17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells.
Blood. 103: 1078-84, 2004.
104)  Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD.
A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib.
Blood. 103: 3222-5, 2004.
105)  Isaacs JS, Jung Y, Neckers L.
ARNT promotes oxygen-independent stabilization of hypoxia inducible factor-1 a by modulating an Hsp90-dependent regulatory pathway.
J Biol Chem. 279: 16128-35, 2004.
106)  Mulshine JL, Neckers L.
Epithelial-directed drug delivery: influence of formulation and delivery devices.
Lung Cancer. 46: 387-92, 2004.
107)  Nielsen TO, Andrews HN, Cheang M, Kucab JE, Hsu FD, Ragaz J, Gilks CB, Makretsov N, Bajdik CD, Brookes C, Neckers LM, Evdokimova V, Huntsman DG, Dunn SE.
Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin.
Cancer Res. 64: 286-91, 2004.
108)  Eustace BK, Sakurai T, Stewart JK, Yimlamai D, Unger C, Zehetmeier C, Lain B, Torella C, Henning SW, Beste G, Scroggins BT, Neckers L, Ilag LL, Jay DG.
Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness.
Nat Cell Biol. 6: 507-14, 2004.
109)  Linehan WM, Vasselli J, Srinivasan R, Walther MM, Merino M, Choyke P, Vocke C, Schmidt L, Isaacs JS, Glenn G, Toro J, Zbar B, Bottaro D, Neckers L.
Genetic basis of cancer of the kidney: disease-specific approaches to therapy.
Clin. Cancer Res. 10: 6282S-9S, 2004.
110)  Kaufman B, Scharf O, Arbeit J, Ashcroft M, Brown JM, Bruick RK, Chapman JD, Evans SM, Giaccia AJ, Harris AL, Huang E, Johnson R, Kaelin W, Koch CJ, Maxwell P, Mitchell J, Neckers L, Powis G, Rajendran J, Semenza GL, Simons J, Storkebaum E, Welch MJ, Whitelaw M, Melillo G, Ivy SP.
Proceedings of the Oxygen Homeostasis/Hypoxia Meeting.
Cancer Res. 64: 3350-6, 2004.
111)  Lee YS, Marcu MG, Neckers L.
Quantum chemical calculations and mutational analysis suggest heat shock protein 90 catalyzes trans-cis isomerization of geldanamycin.
Chem Biol. 11: 991-8, 2004.
112)  Mimnaugh EG, Xu W, Vos M, Yuan X, Isaacs JS, Bisht KS, Gius D, Neckers L.
Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity.
Mol Cancer Ther. 3: 551-66, 2004.
113)  Chiosis G, Huezo H, Rosen N, Mimnaugh E, Whitesell L, Neckers L.
17AAG: low target binding affinity and potent cell activity--finding an explanation.
Mol. Cancer Ther. 2: 123-9, 2003.
114)  Neckers L, Lee YS.
Cancer: the rules of attraction.
Nature. 425: 357-9, 2003.
115)  Dai Q, Zhang C, Wu Y, McDonough H, Whaley RA, Godfrey V, Li HH, Madamanchi N, Xu W, Neckers L, Cyr D, Patterson C.
CHIP activates HSF1 and confers protection against apoptosis and cellular stress.
EMBO J. 22: 5446-58, 2003.
116)  Neckers L.
Development of small molecule Hsp90 inhibitors: utilizing both forward and reverse chemical genomics for drug identification.
Curr Med Chem. 10: 733-9, 2003.
117)  Neckers L.
Development of small molecule Hsp90 inhibitors: utilizing both forward and reverse chemical genomics for drug identification.
Curr Med Chem. 10: 733-9, 2003.
118)  Bisht KS, Bradbury CM, Mattson D, Kaushal A, Sowers A, Markovina S, Ortiz KL, Sieck LK, Isaacs JS, Brechbiel MW, Mitchell JB, Neckers LM, Gius D.
Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity.
Cancer Res. 63: 8984-95, 2003.
119)  Neckers L, Ivy SP.
Heat shock protein 90.
Curr Opin Oncol. 15: 419-24, 2003.
120)  Isaacs JS, Xu W, Neckers L.
Heat shock protein 90 as a molecular target for cancer therapeutics.
Cancer Cell. 3: 213-7, 2003.
121)  Jung Y, Isaacs JS, Lee S, Trepel J, Liu ZG, Neckers L.
Hypoxia-inducible factor induction by tumour necrosis factor in normoxic cells requires receptor-interacting protein-dependent nuclear factor kappa B activation.
Biochem. J. 370: 1011-7, 2003.
122)  Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L.
IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis.
FASEB J. 17: 2115-7, 2003.
123)  Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L.
Microtubule disruption utilizes an NFkappa B-dependent pathway to stabilize HIF-1alpha protein.
J. Biol. Chem. 278: 7445-52, 2003.
124)  Ochel HJ, Gademann G, Trepel J, Neckers L.
Modulation of prion protein structural integrity by geldanamycin.
Glycobiology. 13: 655-60, 2003.
125)  Nakamura M, Matsuo T, Stauffer J, Neckers L, Thiele CJ.
Retinoic acid decreases targeting of p27 for degradation via an N-myc-dependent decrease in p27 phosphorylation and an N-myc-independent decrease in Skp2.
Cell Death Differ. 10: 230-9, 2003.
126)  Neckers L.
Screening for inducers of kinase degradation.
Chem. Biol. 10: 587-9, 2003.
127)  Marcu MG, Neckers LM.
The C-terminal half of heat shock protein 90 represents a second site for pharmacologic intervention in chaperone function.
Curr Cancer Drug Targets. 3: 343-7, 2003.
128)  Xu W, Yuan X, Jung YJ, Yang Y, Basso A, Rosen N, Chung EJ, Trepel J, Neckers L.
The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells.
Cancer Res. 63: 7777-84, 2003.
129)  Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L.
Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu.
Proc Natl Acad Sci U S A. 99: 12847-52, 2002.
130)  Citri A, Alroy I, Lavi S, Rubin C, Xu W, Grammatikakis N, Patterson C, Neckers L, Fry DW, Yarden Y.
Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy.
EMBO J. 21: 2407-17, 2002.
131)  Neckers L.
Heat shock protein 90 inhibition by 17-allylamino-17- demethoxygeldanamycin: a novel therapeutic approach for treating hormone-refractory prostate cancer.
Clin Cancer Res. 8: 962-6, 2002.
132)  Neckers L.
Heat shock protein 90 is a rational molecular target in breast cancer.
Breast Dis. 15: 53-60, 2002.
133)  Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L.
Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha.
Mol Cell Biol. 22: 8506-13, 2002.
134)  Neckers L, Neckers K.
Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents.
Expert Opin Emerg Drugs. 7: 277-88, 2002.
135)  Neckers L.
Hsp90 inhibitors as novel cancer chemotherapeutic agents.
Trends Mol Med. 8: S55-61, 2002.
136)  Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM.
Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway.
J Biol Chem. 277: 29936-44, 2002.
137)  Xu W, Mimnaugh EG, Kim JS, Trepel JB, Neckers LM.
Hsp90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2.
Cell Stress Chaperones. 7: 91-6, 2002.
138)  Mimnaugh EG, Neckers LM.
Immunoblotting methods for the study of protein ubiquitination.
Methods Mol Biol. 194: 179-203, 2002.
139)  Jung YJ, Isaacs JS, Lee S, Trepel J, Liu ZG, Neckers L.
Microtubule disruption utilizes a NFkB-dependent pathway to upregulate HIF-1alpha protein.
J. Biol. Chem. In Press, 2002.
140)  Yu X, Guo ZS, Marcu MG, Neckers L, Nguyen DM, Chen GA, Schrump DS.
Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228.
J Natl Cancer Inst. 94: 504-13, 2002.
141)  Bonvini P, Trepel JB, Neckers LM.
beta-catenin: A potential target for cancer chemotherapy, in Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins.
Humana Press, Inc., Totawa, NJ. L. Bandara & N. LaThangue, eds.: 71-100, 2001.
142)  Mimnaugh EG, Kayastha G, McGovern NB, Hwang SG, Marcu MG, Trepel J, Cai SY, Marchesi VT, Neckers L.
Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli.
Cell Death Differ. 8: 1182-96, 2001.
143)  Yunmbam MK, Li QQ, Mimnaugh EG, Kayastha GL, Yu JJ, Jones LN, Neckers L, Reed E.
Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in human ovarian tumor cells.
Int J Oncol. 19: 741-8, 2001.
144)  Bonvini P, An WG, Rosolen A, Nguyen P, Trepel J, Garcia de Herreros A, Dunach M, Neckers LM.
Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin in melanoma cells, increases beta-catenin-E-cadherin association, and decreases beta-catenin-sensitive transcription.
Cancer Res. 61: 1671-7, 2001.
145)  Li QQ, Yunmbam MK, Zhong X, Yu JJ, Mimnaugh EG, Neckers L, Reed E.
Lactacystin enhances cisplatin sensitivity in resistant human ovarian cancer cell lines via inhibition of DNA repair and ERCC-1 expression.
Cell Mol Biol (Noisy-le-grand). 47 Online Pub: OL61-72, 2001.
146)  Agnew EB, Wilson RH, Grem JL, Neckers L, Bi D, Takimoto CH.
Measurement of the novel antitumor agent 17-(allylamino)-17-demethoxygeldanamycin in human plasma by high-performance liquid chromatography.
J Chromatogr B Biomed Sci Appl. 755: 237-43, 2001.
147)  Casibang M, Purdom S, Jakowlew S, Neckers L, Zia F, Ben-Av P, Hla T, You L, Jablons DM, Moody TW.
Prostaglandin E2 and vasoactive intestinal peptide increase vascular endothelial cell growth factor mRNAs in lung cancer cells.
Lung Cancer. 31: 203-12, 2001.
148)  Isaacs JS, Saito S, Neckers LM.
Requirement for HDM2 activity in the rapid degradation of p53 in neuroblastoma.
J Biol Chem. 276: 18497-506, 2001.
149)  Xu W, Mimnaugh E, Rosser MF, Nicchitta C, Marcu M, Yarden Y, Neckers L.
Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90.
J Biol Chem. 276: 3702-8, 2001.
150)  Soga S, Sharma SV, Shiotsu Y, Shimizu M, Tahara H, Yamaguchi K, Ikuina Y, Murakata C, Tamaoki T, Kurebayashi J, Schulte TW, Neckers LM, Akinaga S.
Stereospecific antitumor activity of radicicol oxime derivatives.
Cancer Chemother Pharmacol. 48: 435-45, 2001.
151)  Blagosklonny MV, Fojo T, Bhalla KN, Kim JS, Trepel JB, Figg WD, Rivera Y, Neckers LM.
The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukemia cells to cytotoxic chemotherapy.
Leukemia. 15: 1537-43, 2001.
152)  Neckers LM.
Can the heat shock protein 90 inhibitor geldanamycin be designed to specifically inhibit HER-2 tyrosine kinase.
Drug Resist Updat. 3: 203-205, 2000.
153)  Lewis J, Devin A, Miller A, Lin Y, Rodriguez Y, Neckers L, Liu ZG.
Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation.
J Biol Chem. 275: 10519-26, 2000.
154)  Neckers L.
Effects of geldanamycin and other naturally occurring small molecule antagonists of heat shock protein 90 on HER2 protein expression.
Breast Dis. 11: 49-59, 2000.
155)  Garayoa M, Martínez A, Lee S, Pío R, An WG, Neckers L, Trepel J, Montuenga LM, Ryan H, Johnson R, Gassmann M, Cuttitta F.
Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis.
Mol Endocrinol. 14: 848-62, 2000.
156)  Shiotsu Y, Neckers LM, Wortman I, An WG, Schulte TW, Soga S, Murakata C, Tamaoki T, Akinaga S.
Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr-Abl with Hsp90 complex.
Blood. 96: 2284-91, 2000.
157)  Marcu MG, Schulte TW, Neckers L.
Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins.
J. Natl. Cancer Inst. 92: 242-8, 2000.
158)  Bonvini P, Hwang SG, El-Gamil M, Robbins P, Kim JS, Trepel J, Neckers L.
Nuclear beta-catenin displays GSK-3beta- and APC-independent proteasome sensitivity in melanoma cells.
Biochim Biophys Acta. 1495: 308-18, 2000.
159)  Mimnaugh EG, Yunmbam MK, Li Q, Bonvini P, Hwang SG, Trepel J, Reed E, Neckers L.
Prevention of cisplatin-DNA adduct repair and potentiation of cisplatin-induced apoptosis in ovarian carcinoma cells by proteasome inhibitors.
Biochem Pharmacol. 60: 1343-54, 2000.
160)  An WG, Schulte TW, Neckers LM.
The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome.
Cell Growth Differ. 11: 355-60, 2000.
161)  Marcu MG, Chadli A, Bouhouche I, Catelli M, Neckers LM.
The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone.
J Biol Chem. 275: 37181-6, 2000.
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This page was last updated on 4/25/2013.