Article (Scientific journals)
Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells.
Umelo, Ijeoma; Wever, Olivier De; Kronenberger, Peter et al.
2015In Lung Cancer, 90 (2), p. 167-74
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Keywords :
Afatinib; EGFR; Invasion; Non-small cell lung cancer; ROCK; Y-27632
Abstract :
[en] INTRODUCTION: Lung cancer remains the leading cause of cancer-related mortality worldwide, with metastatic disease frequently a prominent feature at the time of diagnosis. The role of NSCLC-derived EGFR mutations in cancer cell proliferation and survival has been widely reported, but little is known about the function of these mutations in invasive growth and metastasis. In this study, we sought to evaluate the intrinsic invasive properties of NSCLC cells with differing EGFR status and examine possible therapeutic targets that can abrogate invasive growth. MATERIALS AND METHODS: Collagen-based assays and 3D cell cultures were used to assess morphological features, actin cytoskeleton dynamics and the invasive capacity of NSCLC cell lines with differing EGFR status. The role of the RhoA/ROCK/MYPT1 and EGFR/HER pathways in NSCLC-related invasion was investigated by pharmacological inhibition and RNA interference techniques. RESULTS: We demonstrate a positive correlation between EGFR mutational/amplification status and invasive capacity. Knockdown of wild-type and mutant EGFR leads to depletion of active and total MYPT1 levels. Combined pharmacological inhibition or genetic ablation of ROCK/EGFR suppresses the hallmarks of cancer cells and abrogates the invasive phenotype in EGFR-dependent NSCLC cells. CONCLUSIONS: These observations suggest that combined targeting of the ROCK and EGFR/HER pathways may be a potential therapeutic approach in limiting invasive growth in NSCLC.
Disciplines :
Oncology
Author, co-author :
Umelo, Ijeoma ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Wever, Olivier De
Kronenberger, Peter
Noor, Alfiah
Teugels, Erik
Chen, Gang
Bracke, Marc
Greve, Jacques De
Language :
English
Title :
Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells.
Publication date :
2015
Journal title :
Lung Cancer
ISSN :
0169-5002
eISSN :
1872-8332
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
90
Issue :
2
Pages :
167-74
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
Available on ORBi :
since 06 June 2016

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