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Molecular Cancer
Published in: Molecular Cancer 1/2012

Open Access 01-12-2012 | Research

Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival

Authors: Chad R Schultz, William A Golembieski, Daniel A King, Stephen L Brown, Chaya Brodie, Sandra A Rempel

Published in: Molecular Cancer | Issue 1/2012

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Abstract

Background

The current treatment regimen for glioma patients is surgery, followed by radiation therapy plus temozolomide (TMZ), followed by 6 months of adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of all surgically treated GBM patients remains dismal, and additional or different therapies are required. Depending on the cancer type, SPARC has been proposed both as a therapeutic target and as a therapeutic agent. In glioma, SPARC promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT interact to regulate the activity of each other, we determined whether inhibition of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit both SPARC-induced glioma cell invasion and survival.

Results

Our studies found the following. 1) SPARC increases the expression of tumor cell pro-survival and pro-death protein signaling in balance, and, as a net result, tumor cell survival remains unchanged. 2) Suppressing SPARC increases tumor cell survival, indicating it is not a good therapeutic target. 3) Suppressing HSP27 decreases tumor cell survival in all gliomas, but is more effective in SPARC-expressing tumor cells due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling. 4) Suppressing total AKT1/2 paradoxically enhanced tumor cell survival, indicating that AKT1 or 2 are poor therapeutic targets. 5) However, inhibiting pAKT suppresses tumor cell survival. 6) Inhibiting both HSP27 and pAKT synergistically decreases tumor cell survival. 7) There appears to be a complex feedback system between SPARC, HSP27, and AKT. 8) This interaction is likely influenced by PTEN status. With respect to chemosensitization, we found the following. 1) SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2) Despite this enhanced signaling, SPARC protects cells against TMZ. 3) This protection can be reduced by inhibiting pAKT. 4) Combined inhibition of HSP27 and pAKT is more effective than TMZ treatment alone.

Conclusions

We conclude that inhibition of HSP27 alone, or in combination with pAKT inhibitor IV, may be an effective therapeutic approach to inhibit SPARC-induced glioma cell invasion and survival in SPARC-positive/PTEN-wildtype and SPARC-positive/PTEN-null tumors, respectively.
Appendix
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Literature
1.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007, 114: 97-109. 10.1007/s00401-007-0243-4PubMedCentralCrossRefPubMed
2.
3.
, : Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008, 455: 1061-1068. 10.1038/nature07385CrossRef
4.
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G: An integrated genomic analysis of human glioblastoma multiforme. Science. 2008, 321: 1807-1812. 10.1126/science.1164382PubMedCentralCrossRefPubMed
5.
Brennan C, Momota H, Hambardzumyan D, Ozawa T, Tandon A, Pedraza A, Holland E: Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One. 2009, 4: e7752- 10.1371/journal.pone.0007752PubMedCentralCrossRefPubMed
6.
Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller R, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O'Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, : Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF. Cancer Cell. 2010, 17: 98-110. 10.1016/j.ccr.2009.12.020PubMedCentralCrossRefPubMed
7.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, , : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005, 352: 987-996. 10.1056/NEJMoa043330CrossRefPubMed
8.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005, 352: 997-1003. 10.1056/NEJMoa043331CrossRefPubMed
9.
Polley MY, Lamborn KR, Chang SM, Butowski N, Clarke JL, Prados M: Six-month progression-free survival as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma patients receiving temozolomide. Neuro Oncol. 2010, 3: 274-382.CrossRef
10.
Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, Scheie D, Vik A, Meling TR: Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand. 2010, 122: 159-167. 10.1111/j.1600-0404.2010.01350.xCrossRefPubMed
11.
Sage EH, Johnson C, Bornstein P: Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem. 1984, 259: 3993-4007.PubMed
12.
Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR: Osteonectin, a bone-specific protein linking mineral to collagen. Cell. 1981, 26: 99-105. 10.1016/0092-8674(81)90037-4CrossRefPubMed
13.
Mann K, Deutzmann M, Paulsson R, Timpl R: Solubilization of protein BM-40 from a basement membrane tumor with chelating agents and evidence for its identity with osteonectin and SPARC. FEBS Lett. 1987, 218: 167-172. 10.1016/0014-5793(87)81040-2CrossRefPubMed
14.
Brekken RA, Sage EH: SPARC, a matricellular protein: at the crossroads of cell-matrix communication. Matrix Biol. 2001, 19: 815-827. 10.1016/S0945-053X(00)00133-5CrossRef
15.
Bornstein P, Sage EH: Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol. 2002, 14: 608-616. 10.1016/S0955-0674(02)00361-7CrossRefPubMed
16.
Tai IT, Tang MJ: SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug Resist Updat. 2008, 11: 231-246. 10.1016/j.drup.2008.08.005CrossRefPubMed
17.
Barker TH, Baneyx G, Cardo-Vila M, Workman GA, Weaver M, Menon PM, Dedhar S, Rempel SA, Arap W, Pasqualini R, Vogel V, Sage EH: SPARC regulates cell-matrix interaction through direct binding to integrin-linked kinase. J Biol Chem. 2005, 280: 36483-36493. 10.1074/jbc.M504663200CrossRefPubMed
18.
Nie J, Chang B, Traktuev DO, Sun J, March K, Chan L, Sage EH, Pasqualini R, Arap W, Kolonin MG: IFATS collection: Combinatorial peptides identify alpha5beta1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells. Stem Cells. 2008, 26: 2735-2745. 10.1634/stemcells.2008-0212PubMedCentralCrossRefPubMed
19.
Bos TJ, Cohn SL, Kleinman HK, Murphy-Ulrich JE, Podhajcer OL, Rempel SA, Rich JN, Rutka JT, Sage EH, Thompson EW: International Hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions. Meeting summary. Matrix Biol. 2004, 23: 64-70.CrossRef
20.
Miyoshi K, Sato N, Ohuchida K, Mizumoto K, Tanaka M: SPARC mRNA expression as a prognostic marker for pancreatic adenocarcinoma patients. Anticancer Res. 2010, 30: 867-871.PubMed
21.
Zhao ZS, Wang YY, Chu YQ, Ye ZY, Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2010, 16: 260-268. 10.1158/1078-0432.CCR-09-1247CrossRefPubMed
22.
Taghizadeh F, Tang MJ, Tai IT: Synergism between vitamin D and secreted protein acidic and rich in cysteine-induced apoptosis and growth inhibition results in increased susceptibility of therapy-resistant colorectal cancer cells to chemotherapy. Mol Cancer Ther. 2007, 1: 309-317.CrossRef
23.
Tang MJ, Tai IT: A novel interaction between procaspase 8 and SPARC enhances apoptosis and potentiates chemotherapy sensitivity in colorectal cancers. J Biol Chem. 2007, 282: 34457-34467. 10.1074/jbc.M704459200CrossRefPubMed
24.
Bull Phelps SL, Carbon J, Miller A, Castro-Rivera E, Arnold S, Brekken RA, Lea JS: Secreted protein acidic and rich in cysteine as a regulator of murine cancer growth and chemosensitivity. Am J Obstet Gynecol. 2009, 200: 180e1-180e7.CrossRef
25.
Rempel SA, Golembieski WA, Ge S, Lemke N, Elisevich K, Mikkelsen T, Gutierrez JA: SPARC: a signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas. J Neuropathol Exp Neurol. 1998, 57: 1112-1121. 10.1097/00005072-199812000-00002CrossRefPubMed
26.
Capper D, Mittelbronn M, Goeppert B, Meyermann R, Schittenhelm J: Secreted protein, acidic and rich in cysteine (SPARC) expression in astrocytic tumour cells negatively correlates with proliferation, while vascular SPARC expression is associated with patient survival. Neuropathol Appl Neurobiol. 2010, 36: 183-197. 10.1111/j.1365-2990.2010.01072.xCrossRefPubMed
27.
Golembieski WA, Ge S, Nelson K, Mikkelsen T, Rempel SA: Increased SPARC expression promotes U87 glioblastoma invasion in vitro. Int J Dev Neurosci. 1999, 17: 463-472. 10.1016/S0736-5748(99)00009-XCrossRefPubMed
28.
Golembieski W, Thomas SL, Schultz CR, Yunker CKH, Cazacu S, Barker T, Sage EH, Brodie C, Rempel SA: HSP27 mediates SPARC-induced changes in glioma morphology, migration and invasion. Glia. 2008, 56: 1061-1075. 10.1002/glia.20679CrossRefPubMed
29.
Schultz C, Lemke N, Ge S, Golembieski WA, Rempel SA: Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo. Cancer Res. 2002, 62: 6270-6277.PubMed
30.
Rich JN, Shi Q, Hjelmeland M, Cummings TJ, Kuan CT, Bigner DD, Counter CM, Wang XF: Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. J Biol Chem. 2003, 278: 15951-15957. 10.1074/jbc.M211498200CrossRefPubMed
31.
Guay J, Lambert H, Gingras-Breton G, Lavoie JN, Huot J, Landry J: Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27. J Cell Sci. 1997, 110: 357-368.PubMed
32.
McGregor E, Kempster L, Wait R, Gosling M, Dunn MJ, Powell JT: F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress: a proteonomic approach. Mol Cell Proteomics. 2004, 3: 115-124.CrossRefPubMed
33.
Shi Q, Bao S, Maxwell JA, Reese ED, Friedman HS, Bigner DD, Wang XF, Rich JN: Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through Akt activation. J Biol Chem. 2004, 279: 52200-52209. 10.1074/jbc.M409630200CrossRefPubMed
34.
Weaver MS, Workman G, Sage EH: The copper binding domain of SPARC mediates cell survival in vitro via interaction with integrin β1 and activation of integrin-linked kinase. J Biol Chem. 2008, 283: 22826-22837. 10.1074/jbc.M706563200PubMedCentralCrossRefPubMed
35.
McDonald PC, Fielding AB, Dedhar S: Integrin-linked kinase-essential roles in physiology and cancer biology. J Cell Sci. 2008, 121: 3121-3132. 10.1242/jcs.017996CrossRefPubMed
36.
Shi Q, Bao S, Song L, Wu Q, Bigner DD, Hjelmeland AB, Rich JN: Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Oncogene. 2007, 26: 4084-4094. 10.1038/sj.onc.1210181CrossRefPubMed
37.
Zheng C, Lin Z, Zhao ZJ, Yang Y, Niu H, Shen X: MAPK-activated protein kinase-2 (MK2)-mediated formation and phosphorylation-regulated dissociation of the signal complex consisting of p38, MK2, Akt, and Hsp27. J Biol Chem. 2006, 281: 37215-37226. 10.1074/jbc.M603622200CrossRefPubMed
38.
Wu R, Kausar H, Johnson P, Montoya-Durango DE, Merchant M, Rane MJ: Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex. J Biol Chem. 2007, 282: 21598-21608. 10.1074/jbc.M611316200CrossRefPubMed
39.
Janku F, McConkey DJ, Hong DS, Kurzrock R: Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011, 8: 528-539. 10.1038/nrclinonc.2011.71CrossRefPubMed
40.
Charette SJ, Lavoie JN, Lambert H, Landry J: Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol. 2000, 20: 7602-7612. 10.1128/MCB.20.20.7602-7612.2000PubMedCentralCrossRefPubMed
41.
Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo AP: Hsp27 as a negative regulator of cytochrome C release. Mol Cell Biol. 2002, 22: 816-834. 10.1128/MCB.22.3.816-834.2002PubMedCentralCrossRefPubMed
42.
Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, Diaz-Latoud C, Gurbuxani S, Arrigo AP, Kroemer G, Solary E, Garrido C: HSP27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol. 2000, 2: 645-652. 10.1038/35023595CrossRefPubMed
43.
Garrido C, Bruey JM, Fromentin A, Hammann A, Arrigo AP, Solary E: HSP27 inhibits cytochrome c-dependent activation of procaspase-9. FASEB J. 1999, 13: 2061-2070.PubMed
44.
Concannon CG, Orrenius S, Samali A: Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c. Gene Expr. 2001, 9: 195-201.PubMed
45.
Arya R, Mallik M, Lakhotia SC: Heat shock genes- integrating cell survival and death. J Biosci. 2007, 32: 595-610. 10.1007/s12038-007-0059-3CrossRefPubMed
46.
Roos WP, Batista LF, Naumann SC, Wick W, Weller M, Menck CF, Kaina B: Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine. Oncogene. 2007, 26: 186-197. 10.1038/sj.onc.1209785CrossRefPubMed
47.
Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S: Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004, 11: 448-457. 10.1038/sj.cdd.4401359CrossRefPubMed
48.
Thomas SL, Alam R, Lemke N, Schultz LR, Gutiérrez JA, Rempel SA: PTEN augments SPARC suppression of proliferation and inhibits SPARC-induced migration by suppressing SHC-RAF-ERK and AKT signaling. Neuro Oncol. 2010, 12: 941-955. 10.1093/neuonc/noq048PubMedCentralCrossRefPubMed
49.
Mo HJ, Lee HC, Choi HS, Yang SI: Heat shock-induced, caspase-3-independent rapid breakdown of Akt and consequent alteration of its total phosphorylation/activity level. Biochem Biophys Res Commun. 2000, 276: 702-706. 10.1006/bbrc.2000.3524CrossRefPubMed
50.
Ermoian RP, Furniss CS, Lamborn KR, Basila D, Berger MS, Gottschalk AR, Nicholas MK, Stokoe D, Haas-Kogan DA: Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res. 2002, 8: 1100-1106.PubMed
51.
Wiencke JK, Zheng S, Jelluma N, Tihan T, Vandenberg S, Tamgüney T, Baumber R, Parsons R, Lamborn KR, Berger MS, Wrensch MR, Haas-Kogan DA, Stokoe D: Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neuro Oncol. 2007, 9: 271-279. 10.1215/15228517-2007-003PubMedCentralCrossRefPubMed
52.
Crowell JA, Steele VE, Fay JR: Targeting the AKT protein kinase for cancer chemoprevention. Mol Cancer Ther. 2007, 6: 2139-2148. 10.1158/1535-7163.MCT-07-0120CrossRefPubMed
53.
Chautard E, Loubeau G, Tchirkov A, Chassagne J, Vermot-Desroches C, Morel L, Verrelle P: Akt signaling pathway: a target for radiosensitizing human malignant glioma. Neuro Oncol. 2010, 12: 434-443.PubMedCentralPubMed
54.
55.
Steelman LS, Chappell WH, Abrams SL, Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M, Tafuri A, Bonati A, Bäsecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G, Cervello M, McCubrey JA: Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY). 2011, 3: 192-222.
56.
McKenna LB, Zhou GL, Field J: Isoform-specific functions of Akt in cell motility. Cell Mol Life Sci. 2007, 64: 2723-2725. 10.1007/s00018-007-7247-zCrossRefPubMed
57.
58.
Hara S, Nakashiro K, Goda H, Hamakawa H: Role of Akt isoforms in HGF-induced invasive growth of human salivary gland cancer cells. Biochem Biophys Res Commun. 2008, 370: 123-128. 10.1016/j.bbrc.2008.03.042CrossRefPubMed
59.
Dillon RL, Muller WJ: Distinct biological roles for the akt family in mammary tumor progression. Cancer Res. 2010, 70: 4260-4264. 10.1158/0008-5472.CAN-10-0266PubMedCentralCrossRefPubMed
60.
Mure H, Matsuzaki K, Kitazato KT, Mizobuchi Y, Kuwayama K, Kageji T, Nagahiro S: Akt2 and Akt3 play a pivotal role in malignant gliomas. Neuro Oncol. 2010, 12: 221-232. 10.1093/neuonc/nop026PubMedCentralCrossRefPubMed
61.
Zhang J, Han L, Zhang A, Wang Y, Yue X, You Y, Pu P, Kang C: AKT2 expression is associated with glioma malignant progression and required for cell survival and invasion. Oncol Rep. 2010, 24: 65-72.PubMed
62.
Pu P, Kang C, Li J, Jiang H, Cheng J: The effects of antisense AKT2 RNA on the inhibition of malignant glioma cell growth in vitro and in vivo. J Neurooncol. 2006, 76: 1-11. 10.1007/s11060-005-3029-3CrossRefPubMed
63.
Hammond LA, Eckardt JR, Kuhn JG, Gerson SL, Johnson T, Smith L, Drengler RL, Campbell E, Weiss GR, Von Hoff DD, Rowinsky EK: A randomized phase I and pharmacological trial of sequences of 1, 3-bis(2-chloroethyl)-1-nitrosourea and temozolomide in patients with advanced solid neoplasms. Clin Can Res. 2004, 10: 1645-1656. 10.1158/1078-0432.CCR-03-0174CrossRef
64.
Blough MD, Beauchamp DC, Westgate MR, Kelly JJ, Cairncross JG: Effect of aberrant p53 function on temozolomide sensitivity of glioma cell lines and brain tumor initiating cells from glioblastoma. J Neurooncol. 2011, 102: 1-7. 10.1007/s11060-010-0283-9CrossRefPubMed
65.
Estrugo D, Fischer A, Hess F, Scherthan H, Belka C, Cordes N: Ligand bound beta1 integrins inhibit procaspase-8 for mediating cell adhesion-mediated drug and radiation resistance in human leukemia cells. PLoS One. 2007, 23: e269-CrossRef
66.
Walsh JG, Cullen SP, Sheridan C, Lüthi AU, Gerner C, Martin SJ: Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc Natl Acad Sci USA. 2008, 105: 12815-12819. 10.1073/pnas.0707715105PubMedCentralCrossRefPubMed
67.
Lamkanfi M, Kanneganti TD: Caspase-7: a protease involved in apoptosis and inflammation. Int J Biochem Cell Biol. 2010, 42: 21-24. 10.1016/j.biocel.2009.09.013PubMedCentralCrossRefPubMed
68.
Ang C, Guiot MC, Ramanakumar AV, Roberge D, Kavan P: Clinical significance of molecular biomarkers in glioblastoma. Can J Neurol Sci. 2010, 37: 625-630.CrossRefPubMed
69.
Das P, Puri T, Jha P, Pathak P, Joshi N, Suri V, Sharma MC, Sharma BS, Mahapatra AK, Suri A, Sarkar C: A clinicopathological and molecular analysis of glioblastoma multiforme with long-term survival. J Clin Neurosci. 2011, 18: 66-70. 10.1016/j.jocn.2010.04.050CrossRefPubMed
70.
Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS: Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005, 353: 2012-2024. 10.1056/NEJMoa051918CrossRefPubMed
71.
Brown PD, Krishnan S, Sarkaria JN, Wu W, Jaeckle KA, Uhm JH, Geoffroy FJ, Arusell R, Kitange G, Jenkins RB, Kugler JW, Morton RF, Rowland KM, Mischel P, Yong WH, Scheithauer BW, Schiff D, Giannini C, Buckner JC: Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol. 2008, 26: 5603-5609. 10.1200/JCO.2008.18.0612PubMedCentralCrossRefPubMed
72.
Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MS, McDermott MW, Parsa AT, Vandenberg S, James CD, Lamborn KR, Stokoe D, Haas-Kogan DA: Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol. 2009, 27: 579-584.PubMedCentralCrossRefPubMed
73.
Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, Hoeflich KP, Klumperman J, Friedman LS, Lin K: Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol. 2008, 183: 101-116. 10.1083/jcb.200801099PubMedCentralCrossRefPubMed
74.
Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, Greenman C, Edkins S, Bignell G, Davies H, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Kosmidou V: A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res. 2006, 66: 3987-3991. 10.1158/0008-5472.CAN-06-0127CrossRefPubMed
75.
Rocchi P, Jugpal P, So A, Sinneman S, Ettinger S, Fazli L, Nelson C, Gleave M: Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro. BJU Int. 2006, 98: 1082-1089. 10.1111/j.1464-410X.2006.06425.xCrossRefPubMed
76.
Kamada M, So A, Muramaki M, Rocchi P, Beraldi E, Gleave M: Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther. 2007, 6: 299-308. 10.1158/1535-7163.MCT-06-0417CrossRefPubMed
77.
Matsui Y, Hadaschik BA, Fazli L, Andersen RJ, Gleave ME, So AI: Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Mol Cancer Ther. 2009, 8: 2402-2411. 10.1158/1535-7163.MCT-09-0148CrossRefPubMed
Metadata
Title
Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival
Authors
Chad R Schultz
William A Golembieski
Daniel A King
Stephen L Brown
Chaya Brodie
Sandra A Rempel
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2012
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-11-20

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