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.
β-arrestin1 NSCLC Squamous cell lung cancer Lung adenocarcinoma Prognosis
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The authors thank doctors Lin and Liu of the Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, for their assistance in the processing of tissue sections and the assessment of immunostaining results. This work was supported by Provincial Science and Technology Development Planning of Shandong (2012G0021836), Shandong Provincial Natural Science Foundation of China (ZR2013HZ001), and National Natural Science Foundation of China (81301728).
Compliance with ethical standards
Conflicts of interest
Research involving human participants and/or animals
Our research was approved by Ethical Committee of Shandong Provincial Hospital affiliated to Shandong University.
The informed written consent for the use of their clinical study was obtained from every investigated patients.
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Shenoy SK, Lefkowitz RJ. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmcol Sci. 2011;32:521–33.CrossRefGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
Lymperopoulos A, Bathgate A. Arrestins in the cardiovascular system. Prog Mol Biol Transl Sci. 2013;118:297–334.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar