ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response

Shen,Hongchang; Wang,Liguang; Zhang,Jiangang; Dong,Wei; Zhang,Tiehong; Ni,Yang; Cao,Hongxin; Wang,Kai; Li,Yun; Wang,Yibing; Du,Jiajun

doi:10.3892/or.2016.5337

ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response

Authors:
- Hongchang Shen
- Liguang Wang
- Jiangang Zhang
- Wei Dong
- Tiehong Zhang
- Yang Ni
- Hongxin Cao
- Kai Wang
- Yun Li
- Yibing Wang
- Jiajun Du
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Affiliations: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: December 28, 2016 https://doi.org/10.3892/or.2016.5337
Pages: 761-767
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

ARRB1 (also known as β-arrestin-1) serves as a multifunctional adaptor contributing to the regulation of signaling pathways. ARRB1 may be involved in DNA damage accumulation; however the underlying mechanism involved is unclear. In the present study, non-small cell lung cancer (NSCLC) cell lines (H520 and SK-MES-1) were transfected with ARRB1 plasmids or small interfering ribonucleic acid (siRNA) and received treatment with DNA-damaging agents (cisplatin and etoposide). A mouse xenograft model was used to assess the impact of ARRB1 on the efficacy of cisplatin in vivo. A total of 30 surgically resected NSCLC patients were recruited for the present study and qRT-PCR was performed to determine the mRNA levels in cancer tissues compared with para-carcinoma tissues. Our data showed that DNA damage was abrogated in the ARRB1‑knockdown cells and enhanced in the ARRB1-overexpressing cells. ATR and Chk1 were more activated in the ARRB1-overexpressing cells compared to the ARRB1-knockdown cells, followed by increased H2AX phosphorylation. DNA damage and apoptosis were increased in the ARRB1-overexpressing cells treated with cisplatin. These data provided strong evidence that ARRB1 contributes to the response of NSCLC to DNA-damaging agents and is essential for DNA damage response (DDR). ARRB1 may enhance the efficacy of DNA-damaging agents in NSCLC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
3	Jin F, Zhu H, Shi F, Kong L and Yu J: A retrospective analysis of safety and efficacy of weekly nab-paclitaxel as second-line chemotherapy in elderly patients with advanced squamous non-small-cell lung carcinoma. Clin Interv Aging. 11:167–173. 2016.PubMed/NCBI
4	Tan HL, Ang YL and Soo RA: Therapeutic options in advanced squamous cell lung carcinoma. Lung Cancer. 4:75–86. 2015.
5	Koutsoukos K and Mountzios G: Novel therapies for advanced squamous cell carcinoma of the lung. Future Oncol. 12:659–667. 2016. View Article : Google Scholar : PubMed/NCBI
6	Cufer T and Knez L: Update on systemic therapy of advanced non-small-cell lung cancer. Expert Rev Anticancer Ther. 14:1189–1203. 2014. View Article : Google Scholar : PubMed/NCBI
7	Rothschild SI: Advanced and metastatic lung cancer - what is new in the diagnosis and therapy? Praxis. 104:745–750. 2015.(In German). View Article : Google Scholar : PubMed/NCBI
8	Hosoya N and Miyagawa K: Targeting DNA damage response in cancer therapy. Cancer Sci. 105:370–388. 2014. View Article : Google Scholar : PubMed/NCBI
9	Jackson SP and Bartek J: The DNA-damage response in human biology and disease. Nature. 461:1071–1078. 2009. View Article : Google Scholar : PubMed/NCBI
10	Ciccia A and Elledge SJ: The DNA damage response: Making it safe to play with knives. Mol Cell. 40:179–204. 2010. View Article : Google Scholar : PubMed/NCBI
11	Lefkowitz RJ and Whalen EJ: beta-arrestins: Traffic cops of cell signaling. Curr Opin Cell Biol. 16:162–168. 2004. View Article : Google Scholar : PubMed/NCBI
12	Lefkowitz RJ and Shenoy SK: Transduction of receptor signals by beta-arrestins. Science. 308:512–517. 2005. View Article : Google Scholar : PubMed/NCBI
13	Sobolesky PM and Moussa O: The role of β-arrestins in cancer. Prog Mol Biol Transl Sci. 118:395–411. 2013. View Article : Google Scholar : PubMed/NCBI
14	Ma H, Wang L, Zhang T, Shen H and Du J: Loss of β-arrestin1 expression predicts unfavorable prognosis for non-small cell lung cancer patients. Tumour Biol. 37:1341–1347. 2016. View Article : Google Scholar : PubMed/NCBI
15	Hara MR, Kovacs JJ, Whalen EJ, Rajagopal S, Strachan RT, Grant W, Towers AJ, Williams B, Lam CM, Xiao K, et al: A stress response pathway regulates DNA damage through β₂-adrenoreceptors and β-arrestin-1. Nature. 477:349–353. 2011. View Article : Google Scholar : PubMed/NCBI
16	Hara MR, Sachs BD, Caron MG and Lefkowitz RJ: Pharmacological blockade of a β₂AR-β-arrestin-1 signaling cascade prevents the accumulation of DNA damage in a behavioral stress model. Cell Cycle. 12:219–224. 2013. View Article : Google Scholar : PubMed/NCBI
17	van Engeland M, Nieland LJ, Ramaekers FC, Schutte B and Reutelingsperger CP: Annexin V-affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 31:1–9. 1998. View Article : Google Scholar : PubMed/NCBI
18	Zembruski NC, Stache V, Haefeli WE and Weiss J: 7-Aminoactinomycin D for apoptosis staining in flow cytometry. Anal Biochem. 429:79–81. 2012. View Article : Google Scholar : PubMed/NCBI
19	Patra B, Peng CC, Liao WH, Lee CH and Tung YC: Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device. Sci Rep. 6:210612016. View Article : Google Scholar : PubMed/NCBI
20	Fairbairn DW, Olive PL and O'Neill KL: The comet assay: A comprehensive review. Mutat Res. 339:37–59. 1995. View Article : Google Scholar : PubMed/NCBI
21	Maréchal A and Zou L: DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol. 5:a0127162013. View Article : Google Scholar : PubMed/NCBI
22	Cheng Q and Chen J: Mechanism of p53 stabilization by ATM after DNA damage. Cell Cycle. 9:472–478. 2010. View Article : Google Scholar : PubMed/NCBI
23	Zhou BB and Elledge SJ: The DNA damage response: Putting checkpoints in perspective. Nature. 408:433–439. 2000. View Article : Google Scholar : PubMed/NCBI
24	Kook S, Zhan X, Cleghorn WM, Benovic JL, Gurevich VV and Gurevich EV: Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochromec release and cell death. Cell Death Differ. 21:172–184. 2014. View Article : Google Scholar : PubMed/NCBI
25	Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, Yates JR III and Lefkowitz RJ: Functional specialization of β-arrestin interactions revealed by proteomic analysis. Proc Natl Acad Sci USA. 104:12011–12016. 2007. View Article : Google Scholar : PubMed/NCBI
26	Bernal-Mizrachi L, Lovly CM and Ratner L: The role of NF-κB-1 and NF-κB-2-mediated resistance to apoptosis in lymphomas. Proc Natl Acad Sci USA. 103:9220–9225. 2006. View Article : Google Scholar : PubMed/NCBI
27	Cianfrocca R, Tocci P, Semprucci E, Spinella F, Di Castro V, Bagnato A and Rosanò L: β-Arrestin 1 is required for endothelin-1-induced NF-κB activation in ovarian cancer cells. Life Sci. 118:179–184. 2014. View Article : Google Scholar : PubMed/NCBI
28	Yu J, Wang L, Zhang T, Shen H, Dong W, Ni Y and Du J: Co-expression of β-arrestin1 and NF-кB is associated with cancer progression and poor prognosis in lung adenocarcinoma. Tumour Biol. 36:6551–6558. 2015. View Article : Google Scholar : PubMed/NCBI
29	Lundgren K, Tobin NP, Lehn S, Stål O, Rydén L, Jirström K and Landberg G: Stromal expression of β-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer. J Mol Diagn. 13:340–351. 2011. View Article : Google Scholar : PubMed/NCBI