Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Tumor Biology
Erschienen in: Tumor Biology 6/2015

01.06.2015 | Research Article

Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in colon cancer cells

verfasst von: Yu-Jia Chang, Chien-Yu Huang, Chin-Sheng Hung, Hui-Hsiung Liu, Po-Li Wei

Erschienen in: Tumor Biology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Glucose-regulated protein 78 (GRP78) is expressed as part of the molecular response to endoplasmic reticulum (ER) stress and mediates protein folding within the cell. GRP78 is also an important biomarker of cancer progression and the therapeutic response of patients with different cancer types. However, the role of GRP78 in the cytotoxic effect of 17-DMAG in colon cancer cells remains unclear. GRP78 expression was knocked down by small interfering RNA (siRNA). The anticancer effects of 17-DMAG were assessed by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell-cycle analysis, and an Annexin V-propidium iodide (PI) apoptotic assay. We found that HT-29 cells expressed a lower level of GRP78 compared with DLD-1 cells. The MTT assay revealed that HT-29 cells were more sensitive to 17-DMAG treatment than DLD-1 cells. GRP78 knock down (GRP78KD) cells demonstrated an increased sensitivity to 17-DMAG treatment compared with the scrambled control cells. Based on the cell-cycle analysis and Annexin V-PI apoptotic assay, apoptosis dramatically increased in GRP78KD cells compared with scrambled control DLD-1 cells after these cells were treated with 17-DMAG. Finally, we observed a decrease in the level of Bcl-2 and an increase in the levels of Bad and Bax in GRP78KD cells treated with 17-DMAG. These results are consistent with an increased sensitivity to 17-DMAG after knock down of GRP78. The level of GRP78 expression may determine the therapeutic efficacy of 17-DMAG against colon cancer cells.
Literatur
1.
Binefa G, Rodriguez-Moranta F, Teule A, Medina-Hayas M. Colorectal cancer: from prevention to personalized medicine. World J Gastroenterol WJG. 2014;20:6786–808.CrossRefPubMed
2.
Van Loon K, Venook AP. Adjuvant treatment of colon cancer: what is next? Curr Opin Oncol. 2011;23:403–9.CrossRefPubMed
3.
4.
Whitesell L, Lindquist SL. Hsp90 and the chaperoning of cancer. Nat Rev Cancer. 2005;5:761–72.CrossRefPubMed
5.
McClellan AJ, Xia Y, Deutschbauer AM, Davis RW, Gerstein M, Frydman J. Diverse cellular functions of the hsp90 molecular chaperone uncovered using systems approaches. Cell. 2007;131:121–35.CrossRefPubMed
6.
da Silva VC, Ramos CH. The network interaction of the human cytosolic 90 kDa heat shock protein Hsp90: a target for cancer therapeutics. J Proteome. 2012;75:2790–802.CrossRef
7.
Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18:64–76.CrossRef
8.
Maloney A, Workman P. Hsp90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther. 2002;2:3–24.CrossRefPubMed
9.
Hostein I, Robertson D, DiStefano F, Workman P, Clarke PA. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res. 2001;61:4003–9.PubMed
10.
Basso AD, Solit DB, Chiosis G, Giri B, Tsichlis P, Rosen N. Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J Biol Chem. 2002;277:39858–66.CrossRefPubMed
11.
Fujita N, Sato S, Ishida A, Tsuruo T. Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2002;277:10346–53.CrossRefPubMed
12.
Acquaviva J, He S, Zhang C, Jimenez JP, Nagai M, Sang J, et al. FGFR3 translocations in bladder cancer: differential sensitivity to HSP90 inhibition based on drug metabolism. Mol Cancer Res MCR. 2014;12:1042–54.CrossRefPubMed
13.
He K, Zheng X, Zhang L, Yu J. Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax. Mol Cancer Ther. 2013;12:2559–68.CrossRefPubMed
14.
Babchia N, Calipel A, Mouriaux F, Faussat AM, Mascarelli F. 17-AAG and 17-DMAG-induced inhibition of cell proliferation through B-Raf downregulation in WT B-Raf-expressing uveal melanoma cell lines. Invest Ophthalmol Vis Sci. 2008;49:2348–56.CrossRefPubMed
15.
Hertlein E, Wagner AJ, Jones J, Lin TS, Maddocks KJ, Towns 3rd WH, et al. 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. Blood. 2010;116:45–53.CrossRefPubMedPubMedCentral
16.
Messaoudi S, Peyrat JF, Brion JD, Alami M. Recent advances in Hsp90 inhibitors as antitumor agents. Anti Cancer Agents Med Chem. 2008;8:761–82.CrossRef
17.
Hollingshead M, Alley M, Burger AM, Borgel S, Pacula-Cox C, Fiebig HH, et al. In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. Cancer Chemother Pharmacol. 2005;56:115–25.CrossRefPubMed
18.
Pacey S, Wilson RH, Walton M, Eatock MM, Hardcastle A, Zetterlund A, et al. A phase i study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17:1561–70.CrossRef
19.
Lancet JE, Gojo I, Burton M, Quinn M, Tighe SM, Kersey K, et al. Phase i study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia. Leukemia. 2010;24:699–705.CrossRefPubMed
20.
Kummar S, Gutierrez ME, Gardner ER, Chen X, Figg WD, Zajac-Kaye M, et al. 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. 2010;46:340–7.CrossRefPubMed
21.
Hackl C, Lang SA, Moser C, Mori A, Fichtner-Feigl S, Hellerbrand C, et al. Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition. BMC Cancer. 2010;10:668.CrossRefPubMedPubMedCentral
22.
Fukuyo Y, Inoue M, Nakajima T, Higashikubo R, Horikoshi NT, Hunt C, et al. Oxidative stress plays a critical role in inactivating mutant BRAF by geldanamycin derivatives. Cancer Res. 2008;68:6324–30.CrossRefPubMedPubMedCentral
23.
Moser C, Lang SA, Kainz S, Gaumann A, Fichtner-Feigl S, Koehl GE, et al. Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo. Mol Cancer Ther. 2007;6:2868–78.CrossRefPubMed
24.
Ting J, Lee AS. Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation. DNA. 1988;7:275–86.CrossRefPubMed
25.
Lee AS. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001;26:504–10.CrossRefPubMed
26.
Wang M, Wey S, Zhang Y, Ye R, Lee AS. Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid Redox Signal. 2009;11:2307–16.CrossRefPubMedPubMedCentral
27.
Jamora C, Dennert G, Lee AS. Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME. Proc Natl Acad Sci U S A. 1996;93:7690–4.CrossRefPubMedPubMedCentral
28.
Xing X, Lai M, Wang Y, Xu E, Huang Q. Overexpression of glucose-regulated protein 78 in colon cancer. Clin Chim Acta Int J Clin Chem. 2006;364:308–15.CrossRef
29.
Wang Q, He Z, Zhang J, Wang Y, Wang T, Tong S, et al. Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance. Cancer Detect Prev. 2005;29:544–51.CrossRefPubMed
30.
Ranganathan AC, Zhang L, Adam AP, Aguirre-Ghiso JA. Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells. Cancer Res. 2006;66:1702–11.CrossRefPubMedPubMedCentral
31.
Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem. 2003;278:20915–24.CrossRefPubMed
32.
Song MS, Park YK, Lee JH, Park K. Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase C-epsilon/ERK/AP-1 signaling cascade. Cancer Res. 2001;61:8322–30.PubMed
33.
Park HR, Ryoo IJ, Choo SJ, Hwang JH, Kim JY, Cha MR, et al. Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. Toxicology. 2007;229:253–61.CrossRefPubMed
34.
Fu Y, Li J, Lee AS. GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Res. 2007;67:3734–40.CrossRefPubMed
35.
Chiou JF, Tai CJ, Huang MT, Wei PL, Wang YH, An J, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:603–12.CrossRefPubMed
36.
Chang YJ, Chen WY, Huang CY, Liu HH, Wei PL. Glucose-regulated protein 78 (GRP78) regulates colon cancer metastasis through EMT biomarkers and the NRF-2/HO-1 pathway. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2014.
37.
Wu CT, Wang WC, Chen MF, Su HY, Chen WY, Wu CH, et al. Glucose-regulated protein 78 mediates hormone-independent prostate cancer progression and metastasis through maspin and COX-2 expression. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:195–204.CrossRef
38.
Tai CJ, Wang JW, Su HY, Wang CK, Wu CT, Lien YC, et al. Glucose-regulated protein 94 modulates the therapeutic efficacy to taxane in cervical cancer cells. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:403–10.CrossRef
39.
Chang YJ, Huang CY, Hung CS, Chen WY, Wei PL. GRP78 mediates the therapeutic efficacy of curcumin on colon cancer. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2014.
40.
Chang YJ, Li LT, Chen HA, Hung CS, Wei PL. Silencing survivin activates autophagy as an alternative survival pathway in HCC cells. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:9957–66.CrossRef
41.
Chang YJ, Chiu CC, Wu CH, An J, Wu CC, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1703–9.CrossRefPubMed
42.
Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 1999;13:1211–33.CrossRefPubMed
43.
McMillan DR, Gething MJ, Sambrook J. The cellular response to unfolded proteins: intercompartmental signaling. Curr Opin Biotechnol. 1994;5:540–5.CrossRefPubMed
44.
Sidrauski C, Chapman R, Walter P. The unfolded protein response: an intracellular signalling pathway with many surprising features. Trends Cell Biol. 1998;8:245–9.CrossRefPubMed
45.
Pyrko P, Schonthal AH, Hofman FM, Chen TC, Lee AS. The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer Res. 2007;67:9809–16.CrossRefPubMed
46.
Rutkowski DT, Kaufman RJ. That which does not kill me makes me stronger: adapting to chronic ER stress. Trends Biochem Sci. 2007;32:469–76.CrossRefPubMed
47.
Hersey P, Zhang XD. Adaptation to er stress as a driver of malignancy and resistance to therapy in human melanoma. Pigment Cell Melanoma Res. 2008;21:358–67.CrossRefPubMed
48.
Pootrakul L, Datar RH, Shi SR, Cai J, Hawes D, Groshen SG, et al. Expression of stress response protein GRP78 is associated with the development of castration-resistant prostate cancer. Clin Cancer Res. 2006;12:5987–93.CrossRefPubMed
49.
Zheng HC, Takahashi H, Li XH, Hara T, Masuda S, Guan YF, et al. Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol. 2008;39:1042–9.CrossRefPubMed
50.
Lee E, Nichols P, Groshen S, Spicer D, Lee AS. GRP78 as potential predictor for breast cancer response to adjuvant taxane therapy. Int J Cancer. 2011;128:726–31.CrossRefPubMedPubMedCentral
51.
Lee E, Nichols P, Spicer D, Groshen S, Yu MC, Lee AS. GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res. 2006;66:7849–53.CrossRefPubMed
52.
Wang J, Yin Y, Hua H, Li M, Luo T, Xu L, et al. Blockade of GRP78 sensitizes breast cancer cells to microtubules-interfering agents that induce the unfolded protein response. J Cell Mol Med. 2009;13:3888–97.CrossRefPubMedPubMedCentral
53.
Yang L, Yang S, Liu J, Wang X, Ji J, Cao Y, et al. Expression of GRP78 predicts taxane-based therapeutic resistance and recurrence of human gastric cancer. Exp Mol Pathol. 2014;96:235–41.CrossRefPubMed
54.
Kuo LJ, Hung CS, Chen WY, Chang YJ, Wei PL. Glucose-regulated protein 78 silencing down-regulates vascular endothelial growth factor/vascular endothelial growth factor receptor 2 pathway to suppress human colon cancer tumor growth. J Surg Res. 2013;185:264–72.CrossRefPubMed
55.
Recondo Jr G, Diaz-Canton E, de la Vega M, Greco M, Recondo Sr G, Valsecchi ME. Advances and new perspectives in the treatment of metastatic colon cancer. World J Gastrointest Oncol. 2014;6:211–24.CrossRefPubMedPubMedCentral
56.
Xue N, Jin J, Liu D, Yan R, Zhang S, Xiaoming Y, et al. Antiproliferative effect of HSP90 inhibitor Y306zh against pancreatic cancer is mediated by interruption of AKT and MAPK signaling pathways. Curr Cancer Drug Targets. 2014;14(7):671–83.CrossRefPubMed
57.
Erlichman C. Tanespimycin: the opportunities and challenges of targeting heat shock protein 90. Exp Opin Investig Drugs. 2009;18:861–8.CrossRef
58.
Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell. 2008;14:250–62.CrossRefPubMed
59.
Wang H, Song Y, Hao D, Bai M, Jin L, Gu J, et al. Ultrasound-targeted microbubble destruction combined with dual targeting of HSP72 and HSC70 inhibits HSP90 function and induces extensive tumor-specific apoptosis. Int J Oncol. 2014;45:157–64.PubMed
60.
Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25:4798–811.CrossRefPubMed
61.
Jendrossek V. The intrinsic apoptosis pathways as a target in anticancer therapy. Curr Pharm Biotechnol. 2012;13:1426–38.CrossRefPubMed
62.
Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87:99–163.CrossRefPubMed
63.
Wang JY, Sun J, Huang MY, Wang YS, Hou MF, Sun Y, He H, Krishna N, Chiu SJ, Lin S, Yang S, Chang WC. STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression. Oncog 2014.
64.
Pande G, Kumar NA, Manogaran PS. Flow cytometric study of changes in the intracellular free calcium during the cell cycle. Cytometry. 1996;24:55–63.CrossRefPubMed
65.
66.
Roderick HL, Cook SJ. Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer. 2008;8:361–75.CrossRefPubMed
67.
Kim JH, Lkhagvadorj S, Lee MR, Hwang KH, Chung HC, Jung JH, et al. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma. Biochem Biophys Res Commun. 2014;448:76–82.CrossRefPubMed
68.
Umemura M, Baljinnyam E, Feske S, De Lorenzo MS, Xie LH, Feng X, et al. Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PLoS One. 2014;9:e89292.CrossRefPubMedPubMedCentral
69.
El Boustany C, Bidaux G, Enfissi A, Delcourt P, Prevarskaya N, Capiod T. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation. Hepatology. 2008;47:2068–77.CrossRefPubMed
Metadaten
Titel
Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in colon cancer cells
verfasst von
Yu-Jia Chang
Chien-Yu Huang
Chin-Sheng Hung
Hui-Hsiung Liu
Po-Li Wei
Publikationsdatum
01.06.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3076-0

Weitere Artikel der Ausgabe 6/2015

Tumor Biology 6/2015 Zur Ausgabe

Review

The roles of ADAMTS in angiogenesis and cancer

Research Article

Nicotinamide induces apoptosis of F9 mouse teratocarcinoma stem cells by downregulation of SATB1 expression

Research Article

Role of vitamin D receptor gene polymorphisms in pancreatic cancer: a case–control study in China

Research Article

Effects of zoledronic acid and docetaxel on small GTP-binding proteins in prostate cancer

Research Article

The Arg399Gln polymorphism in the XRCC1 gene is associated with increased risk of hematological malignancies

Research Article

A novel tumor suppressor gene in basal cell carcinoma: inhibition of growth factor-2

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise