Regulation of anoikis resistance by NADPH oxidase 4 and epidermal growth factor receptor

被引:46
作者
Kim, Hyeryeong [1 ]
Sung, Jee Young [2 ]
Park, Eun-Kyung [1 ]
Kho, Seongho [1 ]
Koo, Kyung Hee [1 ]
Park, Seog-Yun [3 ]
Goh, Sung-Ho [4 ]
Jeon, Yoon Kyung [5 ]
Oh, Sekyung [6 ]
Park, Byung-Kiu [2 ]
Jung, Yong-Keun [7 ]
Kim, Yong-Nyun [1 ]
机构
[1] Natl Canc Ctr, Div Canc Biol, Comparat Biomed Res Branch, 323 Ilsan Ro, Goyang Si 410769, South Korea
[2] Natl Canc Ctr, Pediat Oncol Branch, Div Translat & Clin Res 2, 323 Ilsan Ro, Goyang Si 410769, South Korea
[3] Natl Canc Ctr, Dept Pathol, 323 Ilsan Ro, Goyang Si 410769, South Korea
[4] Natl Canc Ctr, Canc Genom Branch, 323 Ilsan Ro, Goyang Si 410769, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Pathol, 28 Daehak Ro, Seoul 110779, South Korea
[6] Stanford Univ, Dept Neurol & Neurol Sci, Sch Biol Sci, Biomax Inst,Sch Med, Stanford, CA 94305 USA
[7] Seoul Natl Univ, Sch Biol Sci, Seoul 151747, South Korea
基金
新加坡国家研究基金会;
关键词
anoikis resistance; EGFR; NOX4; ROS; TO-MESENCHYMAL TRANSITION; PANCREATIC-CANCER CELLS; REDOX REGULATION; EPITHELIAL-CELLS; SURVIVAL SIGNALS; UP-REGULATION; TGF-BETA; NOX4; ACTIVATION; EXPRESSION;
D O I
10.1038/bjc.2016.440
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Normal cells are sensitive to anoikis, which is a cell detachment-induced apoptosis. However, cancer cells acquire anoikis resistance that is essential for successful metastasis. This study aimed to demonstrate the function and potential mechanism of NADPH oxidase 4 (NOX4) and EGFR activation in regulating anoikis resistance in lung cancer. Methods: Cells were cultured either in the attached or suspended condition. Cell viability was measured by cell counting and live and dead cell staining. Expression levels of NOX4 and EGFR were measured by PCR and immunoblotting. Reactive oxygen species (ROS) levels were measured by flow cytometry. Effects of NOX4 overexpression or NOX4 knockdown by si-NOX4 on anoikis sensitivity were explored. Levels of NOX4 and EGFR in lung cancer tissues were evaluated by IHC staining. Results: NOX4 was upregulated but EGFR decreased in suspended cells compared with attached cells. Accordingly, ROS levels were increased in suspended cells, resulting in the activation of Src and EGFR. NOX4 knockdown decreased activation of Src and EGFR, and thus sensitised cells to anoikis. NOX4 overexpression increased EGFR levels and attenuated anoikis. NOX4 expression is upregulated and is positively correlated with EGFR levels in the lung cancer patient tissues. Conclusions: NOX4 upregulation confers anoikis resistance by ROS-mediated activation of EGFR and Src, and by maintaining EGFR levels, which is critical for cell survival.
引用
收藏
页码:370 / 381
页数:12
相关论文
共 38 条
[1]   Proteomic and Functional Investigation of the Colon Cancer Relapse-Associated Genes NOX4 and ITGA3 [J].
Bauer, Kerry M. ;
Watts, Tanya N. ;
Buechler, Steven ;
Hummon, Amanda B. .
JOURNAL OF PROTEOME RESEARCH, 2014, 13 (11) :4910-4918
[2]   The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology [J].
Bedard, Karen ;
Krause, Karl-Heinz .
PHYSIOLOGICAL REVIEWS, 2007, 87 (01) :245-313
[3]   Aiding and abetting roles of NOX oxidases in cellular transformation [J].
Block, Karen ;
Gorin, Yves .
NATURE REVIEWS CANCER, 2012, 12 (09) :627-637
[4]   Targeting NADPH oxidases for the treatment of cancer and inflammation [J].
Bonner, Michael Y. ;
Arbiser, Jack L. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2012, 69 (14) :2435-2442
[5]   Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells [J].
Boudreau, Howard E. ;
Casterline, Benjamin W. ;
Rada, Balazs ;
Korzeniowska, Agnieszka ;
Leto, Thomas L. .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 53 (07) :1489-1499
[6]   OPINION Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression [J].
Buchheit, Cassandra L. ;
Weigel, Kelsey J. ;
Schafer, Zachary T. .
NATURE REVIEWS CANCER, 2014, 14 (09) :632-641
[7]   CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation [J].
Chang, C-C ;
Yang, M-H ;
Lin, B-R ;
Chen, S-T ;
Pan, S-H ;
Hsiao, M. ;
Lai, T-C ;
Lin, S-K ;
Jeng, Y-M ;
Chu, C-Y ;
Chen, R-H ;
Yang, P-C ;
Chin, Y. Eugene ;
Kuo, M-L .
CELL DEATH AND DIFFERENTIATION, 2013, 20 (03) :443-455
[8]   Angiotensin II Induces Epithelial-to-Mesenchymal Transition in Renal Epithelial Cells through Reactive Oxygen Species/Src/Caveolin-Mediated Activation of an Epidermal Growth Factor Receptor-Extracellular Signal-Regulated Kinase Signaling Pathway [J].
Chen, Jianchun ;
Chen, Jian-Kang ;
Harris, Raymond C. .
MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (05) :981-991
[9]   Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone [J].
Ding, YX ;
Chen, ZJ ;
Liu, SG ;
Che, DN ;
Vetter, M ;
Chang, CH .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2005, 57 (01) :111-116
[10]   NADPH Oxidase Activation in Pancreatic Cancer Cells Is Mediated through Akt-dependent Up-regulation of p22phox [J].
Edderkaoui, Mouad ;
Nitsche, Claudia ;
Zheng, Ling ;
Pandol, Stephen J. ;
Gukovsky, Ilya ;
Gukovskaya, Anna S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (10) :7779-7787