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Citations to this article

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma
Adam D. Durbin, … , Gregory E. Hannigan, David Malkin
Adam D. Durbin, … , Gregory E. Hannigan, David Malkin
Published May 26, 2009
Citation Information: J Clin Invest. 2009;119(6):1558-1570. https://doi.org/10.1172/JCI37958.
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Research Article

JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma

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Abstract

Although most reports describe the protein kinase integrin-linked kinase (ILK) as a proto-oncogene, occasional studies detail opposing functions in the regulation of normal and transformed cell proliferation, differentiation, and apoptosis. Here, we demonstrated that ILK functions as an oncogene in the highly aggressive pediatric sarcoma alveolar rhabdomyosarcoma (ARMS) and as a tumor suppressor in the related embryonal rhabdomyosarcoma (ERMS). These opposing functions hinge on signaling through a noncanonical ILK target, JNK1, to the proto-oncogene c-Jun. RNAi-mediated depletion of ILK induced activation of JNK and its target, c-Jun, resulting in growth of ERMS cells, whereas in ARMS cells, it led to loss of JNK/c-Jun signaling and suppression of growth both in vitro and in vivo. Ectopic expression of the fusion gene characteristic of ARMS (paired box 3–forkhead homolog in rhabdomyosarcoma [PAX3-FKHR]) in ERMS cells was sufficient to convert them to an ARMS signaling phenotype and render ILK activity oncogenic. Furthermore, restoration of JNK1 in ARMS reestablished a tumor-suppressive function for ILK. These findings indicate what we believe to be a novel effector pathway regulated by ILK, provide a mechanism for interconversion of oncogenic and tumor-suppressor functions of a single regulatory protein based on the genetic background of the tumor cells, and suggest a rationale for tailored therapy of rhabdomyosarcoma based on the different activities of ILK.

Authors

Adam D. Durbin, Gino R. Somers, Michael Forrester, Malgorzata Pienkowska, Gregory E. Hannigan, David Malkin

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Total citations by year

Year: 2024 2021 2020 2019 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 1 1 1 2 1 1 1 3 2 4 2 3 1 23
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (23)

Title and authors Publication Year
HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks
Cassandri M, Porrazzo A, Pomella S, Noce B, Zwergel C, Aiello FA, Vulcano F, Milazzo L, Camero S, Pajalunga D, Spada M, Manzi V, Gravina GL, Codenotti S, Piccione M, Tomaciello M, Signore M, Barillari G, Marchese C, Fanzani A, De Angelis B, Quintarelli C, Vakoc CR, Chen EY, Megiorni F, Locatelli F, Valente S, Mai A, Rota R, Marampon F
Cell Death Discovery 2024
JNK signaling as a target for anticancer therapy
KS Abdelrahman, HA Hassan, SA Abdel-Aziz, AA Marzouk, A Narumi, H Konno, M Abdel-Aziz
Pharmacological reports : PR 2021
KDM3A/Ets1 epigenetic axis contributes to PAX3/FOXO1‐driven and independent disease‐promoting gene expression in fusion‐positive Rhabdomyosarcoma
LM Sobral, HM Hicks, JK Parrish, TS McCann, J Hsieh, A Goodspeed, JC Costello, JC Black, P Jedlicka
Molecular Oncology 2020
Rsu1-dependent control of PTEN expression is regulated via ATF2 and cJun
YC Kim, R Gonzalez-Nieves, ML Cutler
Journal of Cell Communication and Signaling 2019
Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy.
Park H, Yamamoto H, Mohn L, Ambühl L, Kanai K, Schmidt I, Kim KP, Fraccaroli A, Feil S, Junge HJ, Montanez E, Berger W, Adams RH
Nature Communications 2019
EpCAM+ Liver Cancer Stem-Like Cells Exhibiting Autocrine Wnt Signaling Potentially Originate in Cirrhotic Patients: Cancer Stem-Like Cells Originate in Cirrhosis
R Khosla, A Rastogi, G Ramakrishna, V Pamecha, A Mukhopadhyay, M Vasudevan, SK Sarin, N Trehanpati
Stem Cells Translational Medicine 2017
Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells
H Shen, JL Ma, Y Zhang, GL Deng, YL Qu, XL Wu, JX He, S Zhang, S Zeng
World journal of gastroenterology : WJG 2016
Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism
DA Oldridge, AC Wood, N Weichert-Leahey, I Crimmins, R Sussman, C Winter, LD McDaniel, M Diamond, LS Hart, S Zhu, AD Durbin, BJ Abraham, L Anders, L Tian, S Zhang, JS Wei, J Khan, K Bramlett, N Rahman, M Capasso, A Iolascon, DS Gerhard, JM Auvil, RA Young, H Hakonarson, SJ Diskin, AT Look, JM Maris
Nature 2015
JNK Signaling Mediates EPHA2-Dependent Tumor Cell Proliferation, Motility, and Cancer Stem Cell-like Properties in Non-Small Cell Lung Cancer
W Song, Y Ma, J Wang, D Brantley-Sieders, J Chen
Cancer research 2014
A signaling network stimulated by  2 integrin promotes the polarization of lytic granules in cytotoxic cells
M Zhang, ME March, WS Lane, EO Long
Science signaling 2014
Dissecting Integrin-Dependent Regulation of Neural Stem Cell Proliferation in the Adult Brain
C Porcheri, U Suter, S Jessberger
The Journal of neuroscience : the official journal of the Society for Neuroscience 2014
Mutation in integrin-linked kinase (ILK(R211A)) and heat-shock protein 70 comprise a broadly cardioprotective complex
A Traister, M Walsh, S Aafaqi, M Lu, X Dai, MR Henkleman, A Momen, YQ Zhou, M Husain, S Arab, S Piran, G Hannigan, JG Coles
PloS one 2013
Stress-Induced Isoforms of MDM2 and MDM4 Correlate with High-Grade Disease and an Altered Splicing Network in Pediatric Rhabdomyosarcoma
Jacob AG, O'Brien D, Singh RK, Comiskey DF Jr, Littleton RM, Mohammad F, Gladman JT, Widmann MC, Jeyaraj SC, Bolinger C, Anderson JR, Barkauskas DA, Boris-Lawrie K, Chandler DS
Neoplasia (New York, N.Y.) 2013
DYRK2 phosphorylation of human c-Jun and c-Myc controls tumor progression by monitoring the G1/S transition
Naoe Taira, Rei Mimoto, Morito Kurata, Tomoko Yamaguchi, Masanobu Kitagawa, Yoshio Miki, Kiyotsugu Yoshida
Journal of Clinical Investigation 2012
JNK-Induced Apoptosis, Compensatory Growth, and Cancer Stem Cells: Figure 1
F Chen
Cancer research 2012
ILK Induces Cardiomyogenesis in the Human Heart
A Traister, S Aafaqi, S Masse, X Dai, M Li, A Hinek, K Nanthakumar, G Hannigan, JG Coles
PloS one 2012
Advances in pediatric rhabdomyosarcoma characterization and disease model development.
O'Brien D, Jacob AG, Qualman SJ, Chandler DS
Histology and histopathology 2012
Nephroblastoma overexpressed (NOV/CCN3) gene: a paired-domainspecific PAX3-FKHR transcription target that promotes survival and motility in alveolar rhabdomyosarcoma cells
Y Zhang, C Wang
Oncogene 2011
c-Jun N-terminal kinase is involved in the regulation of proliferation and apoptosis by integrin-linked kinase in human retinoblastoma cells
Z Chen, A Yang, C Xu, Y Xing, W Gong, J Li
Graefe's Archive for Clinical and Experimental Ophthalmology 2011
Ethanol-induced HO-1 and NQO1 Are Differentially Regulated by HIF-1α and Nrf2 to Attenuate Inflammatory Cytokine Expression*
SM Yeligar, K Machida, VK Kalra
The Journal of biological chemistry 2010
MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas
E Missiaglia, CJ Shepherd, S Patel, K Thway, G Pierron, K Pritchard-Jones, M Renard, R Sciot, P Rao, O Oberlin, O Delattre, J Shipley
British Journal of Cancer 2010
Integrin signalling adaptors: not only figurants in the cancer story.
Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P
Nature reviews. Cancer 2010
Integrin-linked kinase: both Jekyll and Hyde in rhabdomyosarcoma
Paul C. McDonald1, Shoukat Dedhar1,2, and Charles Keller3
Journal of Clinical Investigation 2009

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