Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair

Oncogene volume 35, pages 4569–4579 (2016)Cite this article

Subjects

Abstract

The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in lung cancer metastasis, remain largely uncharacterized. Here, we report that PARP1 promotes lung adenocarcinoma relapse to the brain and bones by regulating several steps of the metastatic process in a DNA repair-independent manner. We find that PARP1 expression is associated with overall and distant metastasis-free survival in lung adenocarcinoma patients. Consistent with this, genetic knockdown and pharmacological inhibition of PARP1 significantly attenuated the metastatic potential of lung adenocarcinoma cells. Further investigation revealed that PARP1 potentiates lung adenocarcinoma metastasis by promoting invasion, anoikis resistance, extravasation and self-renewal of lung adenocarcinoma cells and also by modifying the brain microenvironment. Finally, we identified S100A4 and CLDN7 as novel transcriptional targets and clinically relevant effectors of PARP1. Collectively, our study not only revealed previously unknown functions of PARP1 in lung adenocarcinoma metastasis but also delineated the molecular mechanisms underlying the pro-metastatic function of PARP1. Furthermore, these findings provide a foundation for the potential use of PARP1 inhibitors as a new treatment option for lung adenocarcinoma patients with elevated PARP1 expression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Kraus WL, Hottiger MO . PARP-1 and gene regulation: progress and puzzles. Mol Aspects Med 2013; 34: 1109–1123.

    Article  CAS  PubMed  Google Scholar 

  2. Huletsky A, de Murcia G, Muller S, Hengartner M, Menard L, Lamarre D et al. The effect of poly(ADP-ribosyl)ation on native and H1-depleted chromatin. A role of poly(ADP-ribosyl)ation on core nucleosome structure. J Biol Chem 1989; 264: 8878–8886.

    CAS  PubMed  Google Scholar 

  3. D’Amours D, Desnoyers S, D'Silva I, Poirier GG . Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 1999; 342 (Pt 2): 249–268.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ogata N, Ueda K, Kawaichi M, Hayaishi O . Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei. J Biol Chem 1981; 256: 4135–4137.

    CAS  PubMed  Google Scholar 

  5. Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG . PARP inhibition: PARP1 and beyond. Nat Rev Cancer 2010; 10: 293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kim MY, Zhang T, Kraus WL . Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 2005; 19: 1951–1967.

    Article  CAS  PubMed  Google Scholar 

  7. Ryu KW, Kim DS, Kraus WL . New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP-ribose) polymerases. Chem Rev 2015; 115: 2453–2481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Poirier GG, de Murcia G, Jongstra-Bilen J, Niedergang C, Mandel P . Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci USA 1982; 79: 3423–3427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Akiyama T, Takasawa S, Nata K, Kobayashi S, Abe M, Shervani NJ et al. Activation of Reg gene, a gene for insulin-producing beta -cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation. Proc Natl Acad Sci USA 2001; 98: 48–53.

    CAS  PubMed  Google Scholar 

  10. Yu W, Ginjala V, Pant V, Chernukhin I, Whitehead J, Docquier F et al. Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. Nat Genet 2004; 36: 1105–1110.

    Article  CAS  PubMed  Google Scholar 

  11. Ju BG, Lunyak VV, Perissi V, Garcia-Bassets I, Rose DW, Glass CK et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science 2006; 312: 1798–1802.

    Article  CAS  PubMed  Google Scholar 

  12. Cohen-Armon M, Visochek L, Rozensal D, Kalal A, Geistrikh I, Klein R et al. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Mol Cell 2007; 25: 297–308.

    Article  CAS  PubMed  Google Scholar 

  13. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913–917.

    Article  CAS  PubMed  Google Scholar 

  14. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434: 917–921.

    Article  CAS  PubMed  Google Scholar 

  15. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015; 33: 244–250.

    Article  CAS  PubMed  Google Scholar 

  16. Nowsheen S, Cooper T, Bonner JA, LoBuglio AF, Yang ES . HER2 overexpression renders human breast cancers sensitive to PARP inhibition independently of any defect in homologous recombination DNA repair. Cancer Res 2012; 72: 4796–4806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell 2011; 19: 664–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brenner JC, Feng FY, Han S, Patel S, Goyal SV, Bou-Maroun LM et al. PARP-1 inhibition as a targeted strategy to treat Ewing’s sarcoma. Cancer Res 2012; 72: 1608–1613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cheng H, Zhang Z, Borczuk A, Powell CA, Balajee AS, Lieberman HB et al. PARP inhibition selectively increases sensitivity to cisplatin in ERCC1-low non-small cell lung cancer cells. Carcinogenesis 2013; 34: 739–749.

    Article  CAS  PubMed  Google Scholar 

  20. Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O et al. Cisplatin resistance associated with PARP hyperactivation. Cancer Res 2013; 73: 2271–2280.

    Article  CAS  PubMed  Google Scholar 

  21. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK . Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer 2014; 14: 535–546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hoffman PC, Mauer AM, Vokes EE . Lung cancer. Lancet 2000; 355: 479–485.

    Article  CAS  PubMed  Google Scholar 

  23. Senra JM, Telfer BA, Cherry KE, McCrudden CM, Hirst DG, O’Connor MJ et al. Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft. Mol Cancer Ther 2011; 10: 1949–1958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Michels J, Vitale I, Senovilla L, Enot DP, Garcia P, Lissa D et al. Synergistic interaction between cisplatin and PARP inhibitors in non-small cell lung cancer. Cell Cycle 2013; 12: 877–883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Minami D, Takigawa N, Takeda H, Takata M, Ochi N, Ichihara E et al. Synergistic effect of olaparib with combination of cisplatin on PTEN-deficient lung cancer cells. Mol Cancer Res 2013; 11: 140–148.

    Article  CAS  PubMed  Google Scholar 

  26. Botling J, Edlund K, Lohr M, Hellwig B, Holmberg L, Lambe M et al. Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin Cancer Res 2013; 19: 194–204.

    Article  CAS  PubMed  Google Scholar 

  27. Tomida S, Takeuchi T, Shimada Y, Arima C, Matsuo K, Mitsudomi T et al. Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis. J Clin Oncol 2009; 27: 2793–2799.

    Article  CAS  PubMed  Google Scholar 

  28. Director’s Challenge Consortium for the Molecular Classification of Lung A, Shedden K, Taylor JM, Enkemann SA, Tsao MS, Yeatman TJ et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 2008; 14: 822–827.

    Article  Google Scholar 

  29. Gyorffy B, Surowiak P, Budczies J, Lanczky A . Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 2013; 8: e82241.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Feld R, Rubinstein LV, Weisenberger TH . Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies. J Clin Oncol 1984; 2: 1352–1358.

    Article  CAS  PubMed  Google Scholar 

  31. Martini N, Bains MS, Burt ME, Zakowski MF, McCormack P, Rusch VW et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995; 109: 120–129.

    Article  CAS  PubMed  Google Scholar 

  32. Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R et al. Metastatic patterns in adenocarcinoma. Cancer 2006; 106: 1624–1633.

    Article  PubMed  Google Scholar 

  33. Nguyen DX, Chiang AC, Zhang XH, Kim JY, Kris MG, Ladanyi M et al. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 2009; 138: 51–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chitale D, Gong Y, Taylor BS, Broderick S, Brennan C, Somwar R et al. An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors. Oncogene 2009; 28: 2773–2783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Frizzell KM, Gamble MJ, Berrocal JG, Zhang T, Krishnakumar R, Cen Y et al. Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells. J Biol Chem 2009; 284: 33926–33938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gupta GP, Massague J . Cancer metastasis: building a framework. Cell 2006; 127: 679–695.

    Article  CAS  PubMed  Google Scholar 

  37. Joyce JA, Pollard JW . Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9: 239–252.

    Article  CAS  PubMed  Google Scholar 

  38. Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC et al. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 2005; 65: 2378–2386.

    Article  CAS  PubMed  Google Scholar 

  39. Simpson CD, Anyiwe K, Schimmer AD . Anoikis resistance and tumor metastasis. Cancer Lett 2008; 272: 177–185.

    Article  CAS  PubMed  Google Scholar 

  40. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445: 111–115.

    Article  CAS  PubMed  Google Scholar 

  41. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1: 313–323.

    Article  CAS  PubMed  Google Scholar 

  42. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 2009; 11: 1487–1495.

    CAS  PubMed  Google Scholar 

  43. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100: 3983–3988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. Identification of human brain tumour initiating cells. Nature 2004; 432: 396–401.

    Article  CAS  PubMed  Google Scholar 

  45. O’Brien CA, Pollett A, Gallinger S, Dick JE . A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106–110.

    Article  PubMed  Google Scholar 

  46. Tulin A, Spradling A . Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science 2003; 299: 560–562.

    Article  CAS  PubMed  Google Scholar 

  47. Kim MY, Mauro S, Gevry N, Lis JT, Kraus WL . NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell 2004; 119: 803–814.

    Article  CAS  PubMed  Google Scholar 

  48. Krishnakumar R, Kraus WL . PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Mol Cell 2010; 39: 736–749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T et al. Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Cancer Sci 2005; 96: 844–857.

    Article  CAS  PubMed  Google Scholar 

  50. Donato R . Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 2003; 60: 540–551.

    Article  CAS  PubMed  Google Scholar 

  51. Hsieh HL, Schafer BW, Weigle B, Heizmann CW . S100 protein translocation in response to extracellular S100 is mediated by receptor for advanced glycation endproducts in human endothelial cells. Biochem Biophys Res Commun 2004; 316: 949–959.

    Article  CAS  PubMed  Google Scholar 

  52. Tsukita S, Furuse M . Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol 1999; 9: 268–273.

    Article  CAS  PubMed  Google Scholar 

  53. Davies MP, Rudland PS, Robertson L, Parry EW, Jolicoeur P, Barraclough R . Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours. Oncogene 1996; 13: 1631–1637.

    CAS  PubMed  Google Scholar 

  54. Saleem M, Kweon MH, Johnson JJ, Adhami VM, Elcheva I, Khan N et al. S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc Natl Acad Sci USA 2006; 103: 14825–14830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Shen W, Chen D, Fu H, Liu S, Sun K, Sun X . S100A4 protects gastric cancer cells from anoikis through regulation of alphav and alpha5 integrin. Cancer Sci 2011; 102: 1014–1018.

    Article  CAS  PubMed  Google Scholar 

  56. Lioni M, Brafford P, Andl C, Rustgi A, El-Deiry W, Herlyn M et al. Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol 2007; 170: 709–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Darido C, Buchert M, Pannequin J, Bastide P, Zalzali H, Mantamadiotis T et al. Defective claudin-7 regulation by Tcf-4 and Sox-9 disrupts the polarity and increases the tumorigenicity of colorectal cancer cells. Cancer Res 2008; 68: 4258–4268.

    Article  CAS  PubMed  Google Scholar 

  58. Dahiya N, Becker KG, Wood WH 3rd, Zhang Y, Morin PJ . Claudin-7 is frequently overexpressed in ovarian cancer and promotes invasion. PLoS One 2011; 6: e22119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chen N, Sato D, Saiki Y, Sunamura M, Fukushige S, Horii A . S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility. Biochem Biophys Res Commun 2014; 447: 459–464.

    Article  CAS  PubMed  Google Scholar 

  60. Cataldo VD, Gibbons DL, Perez-Soler R, Quintas-Cardama A . Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med 2011; 364: 947–955.

    Article  CAS  PubMed  Google Scholar 

  61. Michels J, Adam J, Goubar A, Obrist F, Damotte D, Robin A et al. Negative prognostic value of high levels of intracellular poly(ADP-ribose) in non-small cell lung cancer. Ann Oncol 2015; 26: 2470–2477.

    Article  CAS  PubMed  Google Scholar 

  62. Elser M, Borsig L, Hassa PO, Erener S, Messner S, Valovka T et al. Poly(ADP-ribose) polymerase 1 promotes tumor cell survival by coactivating hypoxia-inducible factor-1-dependent gene expression. Mol Cancer Res 2008; 6: 282–290.

    Article  CAS  PubMed  Google Scholar 

  63. Tentori L, Muzi A, Dorio AS, Bultrini S, Mazzon E, Lacal PM et al. Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity. Eur J Cancer 2008; 44: 1302–1314.

    Article  CAS  PubMed  Google Scholar 

  64. Rodriguez MI, Peralta-Leal A, O’Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J et al. PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLoS Genet 2013; 9: e1003531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lee MH, Na H, Kim EJ, Lee HW, Lee MO . Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1. Oncogene 2012; 31: 5099–5107.

    Article  CAS  PubMed  Google Scholar 

  66. Rodriguez MI, Gonzalez-Flores A, Dantzer F, Collard J, de Herreros AG, Oliver FJ . Poly(ADP-ribose)-dependent regulation of Snail1 protein stability. Oncogene 2011; 30: 4365–4372.

    Article  CAS  PubMed  Google Scholar 

  67. McPhee TR, McDonald PC, Oloumi A, Dedhar S . Integrin-linked kinase regulates E-cadherin expression through PARP-1. Dev Dyn 2008; 237: 2737–2747.

    Article  CAS  PubMed  Google Scholar 

  68. Lonn P, van der Heide LP, Dahl M, Hellman U, Heldin CH, Moustakas A . PARP-1 attenuates Smad-mediated transcription. Mol Cell 2010; 40: 521–532.

    Article  PubMed  Google Scholar 

  69. De Craene B, Berx G . Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013; 13: 97–110.

    Article  CAS  PubMed  Google Scholar 

  70. Doege CA, Inoue K, Yamashita T, Rhee DB, Travis S, Fujita R et al. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature 2012; 488: 652–655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L et al. Tumor self-seeding by circulating cancer cells. Cell 2009; 139: 1315–1326.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Cheung WK, Zhao M, Liu Z, Stevens LE, Cao PD, Fang JE et al. Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell 2013; 23: 725–738.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kim JH, Sharma A, Dhar SS, Lee SH, Gu B, Chan CH et al. UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells. Cancer Res 2014; 74: 1705–1717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Shan L, Li X, Liu L, Ding X, Wang Q, Zheng Y et al. GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation. Oncogene 2014; 33: 3205–3216.

    Article  CAS  PubMed  Google Scholar 

  75. Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C et al. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 2007; 446: 765–770.

    Article  CAS  PubMed  Google Scholar 

  76. Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 2012; 151: 1068–1082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 2011; 17: 867–874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Piccolo SR, Withers MR, Francis OE, Bild AH, Johnson WE . Multiplatform single-sample estimates of transcriptional activation. Proc Natl Acad Sci USA 2013; 110: 17778–17783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim SK, Hwan Kim J, Yun SJ, Kim WJ, Kim SY . APPEX: analysis platform for the identification of prognostic gene expression signatures in cancer. Bioinformatics 2014; 30: 3284–3286.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank for Drs Joan Massagué, Incheol Shin, Michael Davidson and W Lee Kraus for providing NCI-H2030, PC9 and their metastatic derivatives; pBabe-S100A4; mEmerald-Claudin7-C-12 (CLDN7, Addgene plasmid #54041); and PARP1 shRNA constructs and antibody, respectively. We also thank Dr Sun Kyu Kim for help with bioinformatics analysis, Dr David M Helfman for helpful discussion. This research was supported by the Converging Research Center Program (2014048778), the Intelligent Synthetic Biology Center of Global Frontier Project (2011-0031955) funded by the Ministry of Science, ICT & Future Planning, and the Basic Science Research Program through the National Research Foundation of Korea (NRF-2011-0020334).

Author information

Author notes

  1. A-Y Yang, S C Kim and J Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    E-B Choi, A-Y Yang & M-Y Kim

  2. Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC, Choongchung-Buk-do, Republic of Korea

    S C Kim

  3. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    J Lee, J K Choi & C Choi

  4. KAIST Institute for the BioCentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    C Choi & M-Y Kim

Authors
  1. E-B Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A-Y Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S C Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J K Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M-Y Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M-Y Kim.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, EB., Yang, AY., Kim, S. et al. PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair. Oncogene 35, 4569–4579 (2016). https://doi.org/10.1038/onc.2016.3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2016.3

This article is cited by

Search

Advanced search

Quick links