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Tumor Biology

, Volume 35, Issue 2, pp 1233–1238 | Cite as

High cofilin-1 levels correlate with cisplatin resistance in lung adenocarcinomas

  • Matheus Becker
  • Marco Antônio De Bastiani
  • Carolina Beatriz Müller
  • Melissa M. Markoski
  • Mauro Antônio A. Castro
  • Fábio Klamt
Research Article

Abstract

High cofilin-1 levels have been shown to be an accurate prognostic biomarker in non-small cell lung cancer (NSCLC) and a predictive factor in drug resistance. Herein we explore the role of cofilin-1 in cis-diamminedichloroplatinum(II) (cisplatin) resistance. We evaluated cofilin-1 levels in intrinsically cisplatin-resistant A549 (ICR-A549) cells and determined the cisplatin toxicity in A549 cells transiently transfected and overexpressing CFL1 plasmid. Moreover, expression levels (activity) of the CFL1 gene network were analyzed in a cisplatin-resistant human lung adenocarcinoma cell panel. ICR-A549 cells, selected by challenging parental cells with 10-fold drug GI50 value, presented a sixfold increase in cisplatin GI50 value and an increased cofilin-1 immunocontent (P < 0.01). In addition, cells transfected with cofilin-1 became more resistant to cisplatin (P < 0.01). High activity of the CFL1 gene network was found in a cisplatin-resistant adenocarcinoma cell panel (P < 0.01). In vitro evidences suggest that cofilin-1 is a biological predictor of cisplatin resistance, supporting new treatment initiatives based on cofilin-1 levels to guide chemotherapeutic interventions in NSCLC patients.

Keywords

Non-small cell lung cancer Cisplatin resistance Cofilin-1 CFL1 Predictive biomarker 

Notes

Acknowledgments

This work was supported by the Brazilian funds MCT/CNPq Universal (470306/2011-4), PRONEX/FAPERGS (1000274), PRONEM/FAPERGS (11/2032-5), PqG/FAPERGS (2414-2551/12-8), and MCT/CNPq INCT-TM (573671/2008-7). F.K. received a fellowship from MCT/CNPq (303613/2008-4).

Conflicts of interest

None

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e78S–92S.PubMedCrossRefGoogle Scholar
  3. 3.
    Heist RS, Engelman JA. SnapShot: non-small cell lung cancer. Cancer Cell. 2012;21:448–8. e2.Google Scholar
  4. 4.
    Cho WC. Potentially useful biomarkers for the diagnosis, treatment and prognosis of lung cancer. Biomed Pharmacother. 2007;61:515–9.PubMedGoogle Scholar
  5. 5.
    Chen X, Liu Y, Røe OD, Qian Y, Guo R, Zhu L, et al. Gefitinib or erlotinib as maintenance therapy in patients with advanced stage non-small cell lung cancer: a systematic review. PLoS One. 2013;8(3):e59314.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Nana-Sinkam SP, Powell CA. Molecular biology of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e30S–9S.PubMedCrossRefGoogle Scholar
  7. 7.
    Müller CB, de Barros RL, Moreira JCF, Klamt F. Bioinformatics approach for the validation of non-small cell lung cancer biomarkers. Front Biosci. 2011;3:46–50.CrossRefGoogle Scholar
  8. 8.
    Castro MA, Dal-Pizzol F, Zdanov S, Soares M, Müller CB, Lopes FM, et al. CFL1 expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer. Cancer. 2010;116:3645–55.PubMedCrossRefGoogle Scholar
  9. 9.
    Müller CB, de Barros RL, Castro MAA, Lopes FM, Meurer RT, Roehe A, et al. Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application of quantitative method in a retrospective cohort. J Cancer Res Clin Oncol. 2011;137:1309–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Wang W, Eddy R, Condeelis J. The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer. 2009;7:429–40.CrossRefGoogle Scholar
  11. 11.
    Klamt F, Zdanov S, Levine RL, Pariser A, Zhang Y, Zhang B, et al. Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat Cell Biol. 2009;11:1241–6.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Sinha P, Hütter G, Köttgen E, Dietel M, Schadendorf D, Lage H. Increased expression of epidermal fatty acid binding protein, cofilin, and 14-3-3-sigma (stratifin) detected by two-dimensional gel electrophoresis, mass spectrometry and microsequencing of drug-resistant human adenocarcinoma of the pancreas. Electrophoresis. 1999;20(14):2952–60.PubMedCrossRefGoogle Scholar
  13. 13.
    Gunnersen JM, Spirkoska V, Smith PE, Danks RA, Tan SS. Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression. Glia. 2000;32(2):146–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. Differential protein expression profiling by iTRAQ–2DLC–MS/MS of lung cancer cells undergoing epithelial–mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res. 2006;5(5):1143–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Wang W, Mouneimne G, Sidani M, Wyckoff J, Chen X, Makris A, et al. The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors. J Cell Biol. 2006;173(3):395–404.PubMedCrossRefGoogle Scholar
  16. 16.
    Gemma A, Li C, Sugiyama Y, Matsuda K, Seike Y, Kosaihira S, et al. Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database. BMC Cancer. 2006;6:174.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Castro MA, Filho JL, Dalmolin RJ, Sinigaglia M, Moreira JC, Mombach JC, et al. ViaComplex: software for landscape analysis of gene expression networks in genomic context. Bioinformatics. 2009;25(11):1468–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Giroux Leprieur E, Antoine M, Vieira T, Duruisseaux M, Poulot V, Rabbe N, et al. Clinical and molecular features in patients with advanced non-small-cell lung carcinoma refractory to first-line platinum-based chemotherapy. Lung Cancer. 2013;79(2):167–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Crawford S. Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy. Front Pharmacol. 2013;4:68.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Wang LH, Xiang J, Yan M, Zhang Y, Zhao Y, Yue CF, et al. The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the cofilin-F-actin pathway. Cancer Res. 2010;70(22):9118–28.PubMedCrossRefGoogle Scholar
  21. 21.
    Polachini GM, Sobral LM, Mercante AM, Paes-Leme AF, Xavier FCA, Henrique T, et al. Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis. PLoS One. 2012;7(12):e50517.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Yang ZL, Miao X, Xiong L, Zou Q, Yuan Y, Li J, et al. CFL1 and Arp3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinomas of gallbladder. Cancer Invest. 2013;31(2):132–9.PubMedCrossRefGoogle Scholar
  23. 23.
    van Rheenen J, Song X, van Roosmalen W, Cammer M, Chen X, Desmarais V, et al. EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. J Cell Biol. 2007;179(6):1247–59.PubMedCrossRefGoogle Scholar
  24. 24.
    Oser M, Condeelis J. The cofilin activity cycle in lamellipodia and invadopodia. J Cell Biochem. 2009;108(6):1252–62.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Kotiadis VN, Leadsham JE, Bastow EL, Gheeraert A, Whybrew JM, Bard M, et al. Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance. J Cell Sci. 2012;125:2288–99.PubMedCrossRefGoogle Scholar
  26. 26.
    Yan XD, Pan LY, Yuan Y, Lang JH, Mao N. Identification of platinum-resistance associated proteins through proteomic analysis of human ovarian cancer cells and their platinum-resistant sublines. J Proteome Res. 2007;6(2):772–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Wei R, Zhang Y, Shen L, Jiang W, Li C, Zhong M, et al. Comparative proteomic and radiobiological analyses in human lung adenocarcinoma cells. Mol Cell Biochem. 2012;359(1–2):151–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, et al. Molecular mechanisms of cisplatin resistance. Oncogene. 2012;31(15):1869–83.PubMedCrossRefGoogle Scholar
  29. 29.
    Ihnatovych I, Livak M, Reed J, de Lanerolle P, Strakova Z. Manipulating actin dynamics affects human in vitro decidualization. Biol Reprod. 2009;81(1):222–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Samstag Y, Eckerskorn C, Wesselborg S, Henning S, Wallich R, Meuer SC. Costimulatory signals for human T-cell activation induce nuclear translocation of pp 19/cofilin. Proc Natl Acad Sci U S A. 1994;91(10):4494–8.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Nebl G, Meuer SC, Samstag Y. Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. J Biol Chem. 1996;271(42):26276–80.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Matheus Becker
    • 1
    • 2
  • Marco Antônio De Bastiani
    • 1
    • 2
  • Carolina Beatriz Müller
    • 1
    • 2
  • Melissa M. Markoski
    • 3
  • Mauro Antônio A. Castro
    • 2
    • 4
  • Fábio Klamt
    • 1
    • 2
  1. 1.Laboratório de Bioquímica Celular, Departamento de BioquímicaICBS/UFRGSPorto AlegreBrazil
  2. 2.Instituto Nacional de Ciência e Tecnologia-Translacional em Medicina (INCT-TM)Porto AlegreBrazil
  3. 3.Laboratório de Cardiologia Celular e MolecularIC/FUCPorto AlegreBrazil
  4. 4.Hospital de Clínicas de Porto Alegre (HCPA)/UFRGSPorto AlegreBrazil

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