ATF3 Reduces Migration Capacity by Regulation of Matrix Metalloproteinases Via NFB and STAT3 Inhibition in Glioblastoma

Overview

Journal Cell Death Discov

Date 2017 Mar 3

PMID 28250971

Citations 19

Authors

Jessica Guenzle

Louisa J Wolf

Nicklas W C Garrelfs

Jonathan M Goeldner

Nadja Osterberg

Cora R Schindler

Joseph E Saavedra

Astrid Weyerbrock

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is associated with poor survival and a high recurrence rate in patients due to inevitable uncontrolled infiltrative tumor growth. The elucidation of the molecular mechanisms may offer opportunities to prevent relapses. In this study we investigated the role of the activating transcription factor 3 (ATF3) in migration of GBM cells . RNA microarray revealed that gene expression of ATF3 is induced by a variety of chemotherapeutics and experimental agents such as the nitric oxide donor JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate). We found NFB and STAT3 to be downstream targets inhibited by overexpression of ATF3. We demonstrate that ATF3 is directly involved in the regulation of matrix metalloproteinase expression and activation. Overexpression of ATF3 therefore leads to a significantly reduced migration capacity and induction of tissue inhibitors of matrix metalloproteinases. Our study for the first time identifies ATF3 as a potential novel therapeutic target in glioblastoma.

Citing Articles

Activating transcription factor 3 induces oxidative stress and genotoxicity, transcriptionally modulating metastasis-related gene expression in human papillomavirus-infected cervical cancer.

Naderzadeh E, Kargar M, Mokhtari M, Farhadi A Virol J. 2025; 22(1):46.

PMID: 39994644 PMC: 11849226. DOI: 10.1186/s12985-025-02675-0.

Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells.

Kooti A, Abuei H, Jaafari A, Taki S, Saberzadeh J, Farhadi A Thyroid Res. 2024; 17(1):12.

PMID: 39085957 PMC: 11292864. DOI: 10.1186/s13044-024-00202-x.

EPIC-0307-mediated selective disruption of PRADX-EZH2 interaction and enhancement of temozolomide sensitivity to glioblastoma via inhibiting DNA repair and MGMT.

Xin L, Tan Y, Zhu Y, Cui X, Wang Q, Zhao J Neuro Oncol. 2023; 25(11):1976-1988.

PMID: 37279651 PMC: 10628965. DOI: 10.1093/neuonc/noad102.

Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells.

Arsanjani A, Abuei H, Behzad-Behbahani A, Bagheri Z, ArabSolghar R, Farhadi A Infect Agent Cancer. 2022; 17(1):62.

PMID: 36522783 PMC: 9753250. DOI: 10.1186/s13027-022-00475-7.

TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma.

Yang S, Zhao J, Cui X, Zhan Q, Yi K, Wang Q Theranostics. 2022; 12(16):7032-7050.

PMID: 36276638 PMC: 9576613. DOI: 10.7150/thno.74197.

References

Murray G, Duncan M, ONeil P, McKay J, Melvin W, Fothergill J . Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J Pathol. 1998; 185(3):256-61. DOI: 10.1002/(SICI)1096-9896(199807)185:3<256::AID-PATH115>3.0.CO;2-A. View

delaTorre A, Schroeder R, Kuo P . Alteration of NF-kappa B p50 DNA binding kinetics by S-nitrosylation. Biochem Biophys Res Commun. 1997; 238(3):703-6. DOI: 10.1006/bbrc.1997.7279. View

Komatsu K, Nakanishi Y, Nemoto N, Hori T, Sawada T, Kobayashi M . Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas. Brain Tumor Pathol. 2005; 21(3):105-12. DOI: 10.1007/BF02482184. View

Nath N, Chattopadhyay M, Pospishil L, Cieciura L, Goswami S, Kodela R . JS-K, a nitric oxide-releasing prodrug, modulates ß-catenin/TCF signaling in leukemic Jurkat cells: evidence of an S-nitrosylated mechanism. Biochem Pharmacol. 2010; 80(11):1641-9. PMC: 6959133. DOI: 10.1016/j.bcp.2010.08.011. View

Xie J, Xie Y, Chen B, Pan F, Guo J, Zhao Q . ATF3 functions as a novel tumor suppressor with prognostic significance in esophageal squamous cell carcinoma. Oncotarget. 2014; 5(18):8569-82. PMC: 4226705. DOI: 10.18632/oncotarget.2322. View

Shami P, Saavedra J, Wang L, Bonifant C, Diwan B, Singh S . JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity. Mol Cancer Ther. 2003; 2(4):409-17. View

Falcone S, Perrotta C, De Palma C, Pisconti A, Sciorati C, Capobianco A . Activation of acid sphingomyelinase and its inhibition by the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway: key events in Escherichia coli-elicited apoptosis of dendritic cells. J Immunol. 2004; 173(7):4452-63. DOI: 10.4049/jimmunol.173.7.4452. View

Hadler-Olsen E, Winberg J, Uhlin-Hansen L . Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol. 2013; 34(4):2041-51. DOI: 10.1007/s13277-013-0842-8. View

Curran S, Murray G . Matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 1999; 189(3):300-8. DOI: 10.1002/(SICI)1096-9896(199911)189:3<300::AID-PATH456>3.0.CO;2-C. View

10.

Garthwaite J . Concepts of neural nitric oxide-mediated transmission. Eur J Neurosci. 2008; 27(11):2783-802. PMC: 2610389. DOI: 10.1111/j.1460-9568.2008.06285.x. View

11.

Manicone A, McGuire J . Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol. 2007; 19(1):34-41. PMC: 2235912. DOI: 10.1016/j.semcdb.2007.07.003. View

12.

Weyerbrock A, Osterberg N, Psarras N, Baumer B, Kogias E, Werres A . JS-K, a glutathione S-transferase-activated nitric oxide donor with antineoplastic activity in malignant gliomas. Neurosurgery. 2011; 70(2):497-510. PMC: 3253212. DOI: 10.1227/NEU.0b013e31823209cf. View

13.

Nakagawa T, Kubota T, Kabuto M, Sato K, Kawano H, Hayakawa T . Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg. 1994; 81(1):69-77. DOI: 10.3171/jns.1994.81.1.0069. View

14.

Helbig G, Christopherson 2nd K, Bhat-Nakshatri P, Kumar S, Kishimoto H, Miller K . NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem. 2003; 278(24):21631-8. DOI: 10.1074/jbc.M300609200. View

15.

Huang C, Chen J, Wu J, Tsai H, Lin H, Yan Y . Novel link of anti-apoptotic ATF3 with pro-apoptotic CTMP in the ischemic brain. Mol Neurobiol. 2014; 51(2):543-57. DOI: 10.1007/s12035-014-8710-0. View

16.

Visse R, Nagase H . Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003; 92(8):827-39. DOI: 10.1161/01.RES.0000070112.80711.3D. View

17.

Muller P, Vousden K, Norman J . p53 and its mutants in tumor cell migration and invasion. J Cell Biol. 2011; 192(2):209-18. PMC: 3172183. DOI: 10.1083/jcb.201009059. View

18.

Kogias E, Osterberg N, Baumer B, Psarras N, Koentges C, Papazoglou A . Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-π-activated nitric oxide donor PABA/NO in malignant gliomas. Int J Cancer. 2011; 130(5):1184-94. PMC: 3161158. DOI: 10.1002/ijc.26106. View

19.

Contestabile A, Ciani E . Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int. 2004; 45(6):903-14. DOI: 10.1016/j.neuint.2004.03.021. View

20.

Kiziltepe T, Hideshima T, Ishitsuka K, Ocio E, Raje N, Catley L . JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood. 2007; 110(2):709-18. PMC: 1924477. DOI: 10.1182/blood-2006-10-052845. View