Skip to main content
Top
Published in: Tumor Biology 1/2016

01-01-2016 | Original Article

Loss of β-arrestin1 expression predicts unfavorable prognosis for non-small cell lung cancer patients

Authors: Honghai Ma, Liguang Wang, Tiehong Zhang, Hongchang Shen, Jiajun Du

Published in: Tumor Biology | Issue 1/2016

Login to get access

Abstract

We aimed to study the expression status of β-arrestin1 in non-small cell lung cancer (NSCLC) specimens and its clinicopathologic significance. The correlation between β-arrestin1 and the tumor migration biomarker E-cadherin, as well as smoking index were studied. A total of 152 patients with NSCLC who undergone surgery were enrolled. Altogether, 88 lung squamous cell lung cancer (SCC) specimens and 64 adenocarcinoma (ADC) specimens were tested for immunohistochemistry. Patients’ survival was analyzed by the Kaplan–Meier method. Univariate and multivariate analyses were performed to determine independent prognostic factors. Spearman rank correlation test was used to show data associations. For SCC patients, the expression of β-arrestin1 was either lost (56 of 88, 63.6 %) or low (32 of 88, 36.4 %), which was significantly and negatively associated with E-cadherin expression (P = 0.017). The similar correlation existed between smoking index and β-arrestin1 expression (P = 0.044). For ADC patients, the deletion of β-arrestin1 expression was rare (4 of 64, 6.3 %). Loss of β-arrestin1 expression indicated poorer survival for both SCC (P = 0.026) and ADC patients (P = 0.006). β-arrestin1 expression was detected in the other ADC specimens but showed no significant correlation with survival. In SCC patients, the loss expression of β-arrestin1 was frequently observed, and β-arrestin1 expression was significantly correlated with the smoking index and E-cadherin expression, which all indicated β-arrestin1’s significant clinicopathologic role. However, β-arrestin1 was expressed in most ADC patients, but its clinicopathologic role seemed to be obscure and might need further exploration.
Literature
1.
2.
go back to reference Cagle PT, Chirieac LR. Advances in treatment of lung cancer with targeted therapy. Arch Pathol Lab Med. 2012;136:504–9.CrossRefPubMed Cagle PT, Chirieac LR. Advances in treatment of lung cancer with targeted therapy. Arch Pathol Lab Med. 2012;136:504–9.CrossRefPubMed
3.
go back to reference Krupnick JG, Benovic JL. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol. 1998;38:289–319.CrossRefPubMed Krupnick JG, Benovic JL. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol. 1998;38:289–319.CrossRefPubMed
4.
go back to reference Moore CA, Milano SK, Benovic JL. Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol. 2007;69:451–82.CrossRefPubMed Moore CA, Milano SK, Benovic JL. Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol. 2007;69:451–82.CrossRefPubMed
6.
go back to reference Kovacs JJ, Hara MR, Davenport CL, et al. Arrestin development: emerging roles for beta arrestins in developmental signaling pathways. Dev Cell. 2009;17:443–58.CrossRefPubMedPubMedCentral Kovacs JJ, Hara MR, Davenport CL, et al. Arrestin development: emerging roles for beta arrestins in developmental signaling pathways. Dev Cell. 2009;17:443–58.CrossRefPubMedPubMedCentral
7.
go back to reference Ge L, Ly Y, Hollenberg M, DeFea K. Beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem. 2003;278:34418–26.CrossRefPubMed Ge L, Ly Y, Hollenberg M, DeFea K. Beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem. 2003;278:34418–26.CrossRefPubMed
8.
go back to reference Sun Y, Cheng Z, Ma L, et al. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem. 2002;277:49212–9.CrossRefPubMed Sun Y, Cheng Z, Ma L, et al. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem. 2002;277:49212–9.CrossRefPubMed
9.
go back to reference Zoudilova M, Kumar P, Ge L, et al. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem. 2007;282:20634–46.CrossRefPubMed Zoudilova M, Kumar P, Ge L, et al. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem. 2007;282:20634–46.CrossRefPubMed
10.
go back to reference Zoudilova M, Min J, Richards HL, et al. Beta-arrestins scaffold cofilin with chronophin to direct localized actin filament severing and membrane protrusions downstream of protease-activated receptor-2. J Biol Chem. 2010;285:14318–29.CrossRefPubMedPubMedCentral Zoudilova M, Min J, Richards HL, et al. Beta-arrestins scaffold cofilin with chronophin to direct localized actin filament severing and membrane protrusions downstream of protease-activated receptor-2. J Biol Chem. 2010;285:14318–29.CrossRefPubMedPubMedCentral
11.
go back to reference Wang P, DeFea KA. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Biochemistry. 2006;45:9374–85.CrossRefPubMed Wang P, DeFea KA. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Biochemistry. 2006;45:9374–85.CrossRefPubMed
12.
go back to reference Girnita L, Shenoy SK, Sehat B, et al. Beta-arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J Biol Chem. 2005;280:24412–9.CrossRefPubMed Girnita L, Shenoy SK, Sehat B, et al. Beta-arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J Biol Chem. 2005;280:24412–9.CrossRefPubMed
13.
go back to reference Shenoy SK, Lefkowitz RJ. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmcol Sci. 2011;32:521–33.CrossRef Shenoy SK, Lefkowitz RJ. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmcol Sci. 2011;32:521–33.CrossRef
14.
go back to reference Lakshmikanthan V, Zou L, Kim JI, et al. Identification of beta-arrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proc Natl Acad Sci USA. 2009;106:9379–84.CrossRefPubMedPubMedCentral Lakshmikanthan V, Zou L, Kim JI, et al. Identification of beta-arrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proc Natl Acad Sci USA. 2009;106:9379–84.CrossRefPubMedPubMedCentral
15.
go back to reference Michal AM, Peck AR, Tran TH, et al. Differential expression of arrestins is a predictor of breast cancer progression and survival. Breast Cancer Res Treat. 2011;130:791–807.CrossRefPubMedPubMedCentral Michal AM, Peck AR, Tran TH, et al. Differential expression of arrestins is a predictor of breast cancer progression and survival. Breast Cancer Res Treat. 2011;130:791–807.CrossRefPubMedPubMedCentral
16.
go back to reference Wang LG, Su BH, Du JJ. Expression of β-arrestin1 in gastric cardiac adenocarcinoma and its relation with progression. Asian Pacific J Cancer Prev. 2012;13:5671–5.CrossRef Wang LG, Su BH, Du JJ. Expression of β-arrestin1 in gastric cardiac adenocarcinoma and its relation with progression. Asian Pacific J Cancer Prev. 2012;13:5671–5.CrossRef
17.
go back to reference Ueda Y, Neel NF, Schutyser E, et al. Deletion of the COOH-terminal domain of CXC chemokine receptor 4 leads to the down-regulation of cell-to-cell contact, enhanced motility and proliferation in breast carcinoma cells. Cancer Res. 2006;66:5665–565.CrossRefPubMedPubMedCentral Ueda Y, Neel NF, Schutyser E, et al. Deletion of the COOH-terminal domain of CXC chemokine receptor 4 leads to the down-regulation of cell-to-cell contact, enhanced motility and proliferation in breast carcinoma cells. Cancer Res. 2006;66:5665–565.CrossRefPubMedPubMedCentral
18.
go back to reference Rosanò L, Cianfrocca R, Tocci P, et al. β-arrestin-1 is a nuclear transcriptional regulator of endothelin-1-induced β-catenin signaling. Oncogene. 2013;32:5066–77.CrossRefPubMed Rosanò L, Cianfrocca R, Tocci P, et al. β-arrestin-1 is a nuclear transcriptional regulator of endothelin-1-induced β-catenin signaling. Oncogene. 2013;32:5066–77.CrossRefPubMed
19.
20.
go back to reference Lymperopoulos A, Negussie S. β-Arrestins in cardiac G protein-coupled receptor signaling and function: partners in crime or “good cop, bad cop”? Int J Mol Sci. 2013;14:24726–41.CrossRefPubMedPubMedCentral Lymperopoulos A, Negussie S. β-Arrestins in cardiac G protein-coupled receptor signaling and function: partners in crime or “good cop, bad cop”? Int J Mol Sci. 2013;14:24726–41.CrossRefPubMedPubMedCentral
21.
go back to reference Lymperopoulos A, Bathgate A. Arrestins in the cardiovascular system. Prog Mol Biol Transl Sci. 2013;118:297–334.CrossRefPubMed Lymperopoulos A, Bathgate A. Arrestins in the cardiovascular system. Prog Mol Biol Transl Sci. 2013;118:297–334.CrossRefPubMed
22.
go back to reference Hu S, Wang D, Wu J, et al. Involvement of β-arrestins in cancer progression. Mol Biol Rep. 2013;40:1065–71.CrossRefPubMed Hu S, Wang D, Wu J, et al. Involvement of β-arrestins in cancer progression. Mol Biol Rep. 2013;40:1065–71.CrossRefPubMed
23.
go back to reference Dasgupta P, Rastogi S, Pillai S, et al. Nicotine induces cell proliferation by beta-arrestin mediated activation of Src and Rb-Raf-1 pathways. J Clin Invest. 2006;116:2208–17.CrossRefPubMedPubMedCentral Dasgupta P, Rastogi S, Pillai S, et al. Nicotine induces cell proliferation by beta-arrestin mediated activation of Src and Rb-Raf-1 pathways. J Clin Invest. 2006;116:2208–17.CrossRefPubMedPubMedCentral
24.
go back to reference Dasgupta P, Rizwani W, Pillai S, et al. β-arrestin1 mediated regulation of E2F target genes in nicotine-induced growth of lung tumors. J Natl Cancer Inst. 2011;103:317–33.CrossRefPubMedPubMedCentral Dasgupta P, Rizwani W, Pillai S, et al. β-arrestin1 mediated regulation of E2F target genes in nicotine-induced growth of lung tumors. J Natl Cancer Inst. 2011;103:317–33.CrossRefPubMedPubMedCentral
25.
go back to reference Saunders W. Centrosomal amplification and spindle multipolarity in cancer cells. Semin Cancer Biol. 2005;15:25–32.CrossRefPubMed Saunders W. Centrosomal amplification and spindle multipolarity in cancer cells. Semin Cancer Biol. 2005;15:25–32.CrossRefPubMed
26.
go back to reference Doxsey S, Zimmerman W, Mikule K. Centrosome control of the cell cycle. Trends Cell Biol. 2005;15:303–11.CrossRefPubMed Doxsey S, Zimmerman W, Mikule K. Centrosome control of the cell cycle. Trends Cell Biol. 2005;15:303–11.CrossRefPubMed
27.
go back to reference Molla-Herman A, Boularan C, Ghossoub R, et al. Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control. PLoS ONE. 2008;3:e3728.CrossRefPubMedPubMedCentral Molla-Herman A, Boularan C, Ghossoub R, et al. Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control. PLoS ONE. 2008;3:e3728.CrossRefPubMedPubMedCentral
28.
go back to reference Shankar H, Michal A, Kern RC, et al. Non-visual arrestins are constitutively associated with the centrosome and regulate centrosome function. J Biol Chem. 2010;285:8316–9.CrossRefPubMedPubMedCentral Shankar H, Michal A, Kern RC, et al. Non-visual arrestins are constitutively associated with the centrosome and regulate centrosome function. J Biol Chem. 2010;285:8316–9.CrossRefPubMedPubMedCentral
29.
go back to reference Perumal D, Pillai S, Nguyen J, et al. Nicotinic acetylcholine receptors induce c-Kit ligand/stem cell factor and promote stemness in an ARRB1/β-arrestin-1 dependent manner in NSCLC. Oncotarget. 2014;5:10486–502.CrossRefPubMedPubMedCentral Perumal D, Pillai S, Nguyen J, et al. Nicotinic acetylcholine receptors induce c-Kit ligand/stem cell factor and promote stemness in an ARRB1/β-arrestin-1 dependent manner in NSCLC. Oncotarget. 2014;5:10486–502.CrossRefPubMedPubMedCentral
Metadata
Title
Loss of β-arrestin1 expression predicts unfavorable prognosis for non-small cell lung cancer patients
Authors
Honghai Ma
Liguang Wang
Tiehong Zhang
Hongchang Shen
Jiajun Du
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3886-0

Other articles of this Issue 1/2016

Tumor Biology 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine