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Article

Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT

  • Authors:
    • Linshui Zhou
    • Xin Lv
    • Junchao Yang
    • Yuanhong Zhu
    • Zhen Wang
    • Tingzhen Xu
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310006, P.R. China
  • Pages: 2533-2538
    |
    Published online on: June 13, 2018
       https://doi.org/10.3892/ol.2018.8963
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Abstract

Lung cancer is one of the most common malignant tumors and also the leading cause of cancer‑related deaths in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKI), such as gefitinib, have been used in the therapy of lung cancer. However, the acquisition of drug resistance is a major limitation in the clinical efficiency of EGFR‑TKIs. Epithelial‑mesenchymal transition (EMT) has been demonstrated to be an underlying mechanism of acquired resistance. A previous study has reported that Napsin A expression can inhibit EMT in lung cancer cells. The present study therefore investigated the effect of Napsin A on the sensitivity of EGFR‑TKI‑resistant lung cancer cells. First, a drug‑resistant lung cancer cell line was generated using the EGFR‑TKI gefitinib on A549 cells (termed here A549‑GFT). EMT was demonstrated to be induced in the drug resistant A549‑GFT cells, evidenced by reduced E‑cadherin expression and increased Vimentin expression compared with control A549 cells. Next, Napsin A was overexpressed in the cells by transfection of the Napsin A‑expression vector, PLJM1‑Napsin A. Western blot analysis confirmed that the protein expression levels of Napsin A were significantly elevated in the Napsin A‑overexpressing cells. Cell proliferation and apoptosis assays were performed to evaluate the effect of Napsin A overexpression on resistant A549 cells. The results of MTT assay demonstrated that Napsin A overexpression inhibited the proliferation of A549 and drug‑resistant A549‑GFT cells and that the proliferation of Napsin A‑overexpressing A549‑GFT cells was significantly inhibited by gefitinib treatment compared with control A549‑GFT cells. The results from the Annexin V/propidium iodide double staining apoptosis assay indicated that Napsin A overexpression enhanced gefitinib‑induced apoptosis in A549‑GFT cells. Additionally, EMT was reversed following Napsin A expression in A549‑GFT cells, as evidenced by the restoration of E‑cadherin and downregulation of Vimentin expression. Further investigation demonstrated that Napsin A overexpression resulted in inhibition of focal adhesion kinase, a critical factor in integrin signaling, in the resistant A549‑GFT cells. These data suggested that Napsin A resensitized the drug‑resistant A549‑GFT cells to gefitinib, possibly by reversing EMT via integrin signaling inhibition. Therefore, Napsin A combined with a TKI may be a more effective treatment strategy for lung cancer.
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1 

PDQ Adult Treatment Editorial Board: Non-small cell lung cancer treatment (PDQ®): Patient Version, . PDQ cancer information summaries [Internet]. Nat Cancer Inst (US); Bethesda: https://www.ncbi.nlm.nih.gov/books/NBK65917/April 13–2017

2 

Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Soria JC, Mok TS, Cappuzzo F and Jänne PA: EGFR-mutated oncogene-addicted non-small cell lung cancer: Current trends and future prospects. Cancer Treat Rev. 38:416–430. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Nguyen KS and Neal JW: First-line treatment of EGFR-mutant non-small-cell lung cancer: The role of erlotinib and other tyrosine kinase inhibitors. Biologics. 6:337–345. 2012.PubMed/NCBI

5 

Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG and Varmus H: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2:e732005. View Article : Google Scholar : PubMed/NCBI

6 

Wu PF, Zhu YP, Yang CH, Wang YF and Wang GH: The Mechanism and countermeasures on the secondary resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI). Anti-Tumor Pharm. 5:42015.

7 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Robert G, Gaggioli C, Bailet O, Chavey C, Abbe P, Aberdam E, Sabatié E, Cano A, de Herreros Garcia A, Ballotti R and Tartare-Deckert S: SPARC represses E-cadherin and induces mesenchymal transition during melanoma development. Cancer Res. 66:7516–7523. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Voulgari A and Pintzas A: Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 1796:75–90. 2009.PubMed/NCBI

10 

Neel DS and Bivona TG: Secrets of drug resistance in NSCLC exposed by new molecular definition of EMT. Clin Cancer Res. 19:3–5. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Uramoto H, Iwata T, Onitsuka T, Shimokawa H, Hanagiri T and Oyama T: Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma. Anticancer Res. 30:2513–2517. 2010.PubMed/NCBI

12 

Tatnell PJ, Powell DJ, Hill J, Smith TS, Tew DG and Kay J: Napsins: New human aspartic proteinases. Distinction between two closely related genes. FEBS Lett. 441:43–48. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Chuman Y, Bergman A, Ueno T, Saito S, Sakaguchi K, Alaiya AA, Franzén B, Bergman T, Arnott D, Auer G, et al: Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas. FEBS Lett. 462:129–134. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Schauer-Vukasinovic V, Bur D, Kling D, Grüninger F and Giller T: Human napsin A: Expression, immunochemical detection, and tissue localization. FEBS Lett. 462:135–139. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Hirano T, Auer G, Maeda M, Hagiwara Y, Okada S, Ohira T, Okuzawa K, Fujioka K, Franzén B, Hibi N, et al: Human tissue distribution of TA02, which is homologous with a new type of aspartic proteinase, napsin A. Jpn J Cancer Res. 91:1015–1021. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Hirano T, Gong Y, Yoshida K, Kato Y, Yashima K, Maeda M, Nakagawa A, Fujioka K, Ohira T, Ikeda N, et al: Usefulness of TA02 (napsin A) to distinguish primary lung adenocarcinoma from metastatic lung adenocarcinoma. Lung Cancer. 41:155–162. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Ueno T, Linder S and Elmberger G: Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer. 88:1229–1233. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Hirano T, Auer G, Maeda M, Hagiwara Y, Okada S, Ohira T, Okuzawa K, Fujioka K, Franzén B, Hibi N, et al: Human tissue distribution of TA02, which is homologous with a new type of aspartic proteinase, napsin A. Jpn J Cancer Res. 91:1015–1021. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Ueno T, Elmberger G, Weaver TE, Toi M and Linder S: The aspartic protease napsin A suppresses tumor growth independent of its catalytic activity. Lab Invest. 88:256–263. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Meena AS, Sharma A, Kumari R, Mohammad N, Singh SV and Bhat MK: Inherent and acquired resistance to paclitaxel in hepatocellular carcinoma: Molecular events involved. PLoS One. 8:e615242013. View Article : Google Scholar : PubMed/NCBI

21 

Hauck CR, Hsia DA and Schlaepfer DD: The focal adhesion kinase-a regulator of cell migration and invasion. IUBMB Life. 53:115–119. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Xie B, Zhao J, Kitagawa M, Durbin J, Madri JA, Guan JL and Fu XY: Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion. J Biol Chem. 276:19512–19523. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Bhowmick NA, Zent R, Ghiassi M, McDonnell M and Moses HL: Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J Biol Chem. 276:46707–46713. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Zheng JX, Guan SH, Xu Q, Liu JZ and Song P: Inhibition of epithelial-mesenchymal transition in A549 cell by transfected Napsin A. Chin Med J (Engl). 125:2734–2740. 2012.PubMed/NCBI

25 

Hauck CR, Sieg DJ, Hsia DA, Loftus JC, Gaarde WA, Monia BP and Schlaepfer DD: Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. 61:7079–7090. 2001.PubMed/NCBI

26 

Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH and Schlaepfer DD: FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol. 2:249–256. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Sieg DJ, Hauck CR and Schlaepfer DD: Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J Cell Sci. 112:2677–2691. 1999.PubMed/NCBI

28 

Parsons JT, Martin KH, Slack JK, Taylor JM and Weed SA: Focal adhesion kinase: A regulator of focal adhesion dynamics and cell movement. Oncogene. 19:5606–5613. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Ruoslahti E: RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 12:697–715. 1996. View Article : Google Scholar : PubMed/NCBI

30 

Juliano RL: Signal transduction by cell adhesion receptors and the cytoskeleton: Functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. Annu Rev Pharmacol Toxicol. 42:283–323. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Hynes RO: Integrins: Bidirectional, allosteric signaling machines. Cell. 110:673–687. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Li Y, Yang J, Dai C, Wu C and Liu Y: Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest. 112:503–516. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhou L, Lv X, Yang J, Zhu Y, Wang Z and Xu T: Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT. Oncol Lett 16: 2533-2538, 2018.
APA
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., & Xu, T. (2018). Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT. Oncology Letters, 16, 2533-2538. https://doi.org/10.3892/ol.2018.8963
MLA
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., Xu, T."Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT". Oncology Letters 16.2 (2018): 2533-2538.
Chicago
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., Xu, T."Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT". Oncology Letters 16, no. 2 (2018): 2533-2538. https://doi.org/10.3892/ol.2018.8963
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou L, Lv X, Yang J, Zhu Y, Wang Z and Xu T: Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT. Oncol Lett 16: 2533-2538, 2018.
APA
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., & Xu, T. (2018). Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT. Oncology Letters, 16, 2533-2538. https://doi.org/10.3892/ol.2018.8963
MLA
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., Xu, T."Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT". Oncology Letters 16.2 (2018): 2533-2538.
Chicago
Zhou, L., Lv, X., Yang, J., Zhu, Y., Wang, Z., Xu, T."Overexpression of Napsin A resensitizes drug‑resistant lung cancer A549 cells to gefitinib by inhibiting EMT". Oncology Letters 16, no. 2 (2018): 2533-2538. https://doi.org/10.3892/ol.2018.8963
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