Tumor Biology

, Volume 35, Issue 7, pp 6311–6317 | Cite as

Overexpression of HCC1/CAPERα may play a role in lung cancer carcinogenesis

  • Yurong Chai
  • Xinxin Liu
  • Liping Dai
  • Yang Li
  • Mei Liu
  • Jian-Ying Zhang
Research Article


HCC1/CAPERα is considered to be a novel human tumor-associated antigen, and the tumor-specific immunity of HCC1/CAPERα has been reported in several types of cancer. However, there was very limited evidence indicating its function in tumorigenesis. In the present study, to elucidate the roles and underlying molecular mechanism of HCC1/CAPERα in lung cancer, we examined the expression of HCC1/CAPERα in human non-small cell lung cancer (NSCLC) cell line and NSCLC tissue microarray (TMA). Immunohistochemistry with TMA was performed to detect HCC1/CAPERα expression in NSCLC and adjacent lung tissues. NSCLC cell line constitutively transfected by pcDNA3.1-HCC1/CAPERα, and empty pcDNA3.1 vector were used. These cells were analyzed by Western blot, MTT, immunofluorescence, wound healing assay, and transwell assays. It was found that HCC1/CAPERα was mainly localized in the nucleus of the lung cancer cells and overexpression of HCC1/CAPERα may promote lung cancer cells proliferation and increase cells migration. The frequency of HCC1/CAPERα expression in NSCLC tissues was significantly higher than that in adjacent and normal tissues (P < 0.01). Our data suggest that overexpression of HCC1/CAPERα may increase the proliferation and migration of NSCLC cells, and HCC1/CAPERα could be a promising biomarker for lung cancer.


Lung cancer HCC1/CAPERα Biomarker Overexpression Carcinogenesis 



Authors thank Dr. Eng M. Tan (The Scripps Research Institute, La Jolla, CA) for his support to this study. This work was supported by grant (SC1CA166016) from the National Institutes of Health (NIH). We would also like to thank the Border Biomedical Research Center (BBRC) Core facilities at The University of Texas at El Paso (UTEP) for their help, which were funded by NIH grant (5G12MD007592).

Conflicts of interest



  1. 1.
    Tan HT, Lee YH, Chung MC. Cancer proteomics. Mass Spectrom Rev. 2012;31:583–605.CrossRefPubMedGoogle Scholar
  2. 2.
    Tan EM, Zhang J. Autoantibodies to tumor-associated antigens: reporters from the immune system. Immunol Rev. 2008;222:328–40.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Zhang JY, Tan EM. Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert Rev Mol Diagn. 2010;10:321–8.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Soussi T. P53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000;60:1777–88.PubMedGoogle Scholar
  5. 5.
    Looi K, Megliorino R, Shi FD, Peng XX, Chen Y, Zhang JY. Humoral immune response to p16, a cyclin-dependent kinase inhibitor in human malignancies. Onco Rep. 2006;16:1105–10.Google Scholar
  6. 6.
    Zhang JY, Chan EK, Peng XX, Lu M, Wang X, Mueller F, et al. Autoimmune responses to mRNA binding proteins p62 and koc in diverse malignancies. Clin Immunol. 2001;100:149–56.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang JY, Chan EK, Peng XX, Tan EM. A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma. J Exp Med. 1999;189:1101–10.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Soo Hoo L, Zhang JY, Chan EK. Cloning and characterization of a novel 90 kda 'companion' auto-antigen of p62 overexpressed in cancer. Oncogene. 2002;21:5006–15.CrossRefPubMedGoogle Scholar
  9. 9.
    Tan EM. Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis. J Clin Invest. 2001;108:1411–5.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Valcarcel J, Gaur RK, Singh R, Green MR. Interaction of u2af65 rs region with pre-mrna branch point and promotion of base pairing with u2 snRNA [corrected]. Science. 1996;273:1706–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Rappsilber J, Ryder U, Lamond AI, Mann M. Large-scale proteomic analysis of the human spliceosome. Genome Res. 2002;12:1231–45.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Jung DJ, Na SY, Na DS, Lee JW. Molecular cloning and characterization of caper, a novel coactivator of activating protein-1 and estrogen receptors. J Biol Chem. 2002;277:1229–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Dowhan DH, Hong EP, Auboeuf D, Dennis AP, Wilson MM, Berget SM, et al. Steroid hormone receptor coactivation and alternative RNA splicing by u2af65-related proteins caperalpha and caperbeta. Mol Cell. 2005;17:429–39.CrossRefPubMedGoogle Scholar
  14. 14.
    Dutta J, Fan G, Gelinas C. Caperalpha is a novel rel-tad-interacting factor that inhibits lymphocyte transformation by the potent rel/nf-kappab oncoprotein v-rel. J Virol. 2008;82:10792–802.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Imai H, Chan EK, Kiyosawa K, Fu XD, Tan EM. Novel nuclear autoantigen with splicing factor motifs identified with antibody from hepatocellular carcinoma. J Clin Invest. 1993;92:2419–26.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  18. 18.
    Bangur CS, Switzer A, Fan L, Marton MJ, Meyer MR, Wang T. Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis. Oncogene. 2002;21:3814–25.CrossRefPubMedGoogle Scholar
  19. 19.
    Mercier I, Casimiro MC, Zhou J, Wang C, Plymire C, Bryant KG, et al. Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of dcis-like mammary lesions. Am J Pathol. 2009;174:1172–90.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Chen Y, Zhou Y, Qiu S, Wang K, Liu S, Peng XX, et al. Autoantibodies to tumor-associated antigens combined with abnormal alpha-fetoprotein enhance immunodiagnosis of hepatocellular carcinoma. Cancer Lett. 2010;289:32–9.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Shao Q, Ren P, Li Y, Peng B, Dai L, Lei N, et al. Autoantibodies against glucose-regulated protein 78 as serological diagnostic biomarkers in hepatocellular carcinoma. Int J Oncol. 2012;41:1061–7.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.CrossRefPubMedGoogle Scholar
  23. 23.
    Liu X, Chai Y, Li J, Ren P, Liu M, Dai L, et al. Autoantibody response to a novel tumor-associated antigen p90/cip2a in breast cancer immunodiagnosis. Tumor Biol. 2014. doi: 10.1007/s13277-013-1350-6.
  24. 24.
    Tan EM, Chan EK, Sullivan KF, Rubin RL. Antinuclear antibodies (ANAs): diagnostically specific immune markers and clues toward the understanding of systemic autoimmunity. Clin Immunol Immunopathol. 1988;47:121–41.CrossRefPubMedGoogle Scholar
  25. 25.
    Tan EM. Autoantibodies in pathology and cell biology. Cell. 1991;67:841–2.CrossRefPubMedGoogle Scholar
  26. 26.
    Lamond AI. The spliceosome. BioEssays. 1993;15:595–603.CrossRefPubMedGoogle Scholar
  27. 27.
    Nagai K, Oubridge C, Jessen TH, Li J, Evans PR. Crystal structure of the RNA-binding domain of the u1 small nuclear ribonucleoprotein a. Nature. 1990;348:515–20.CrossRefPubMedGoogle Scholar
  28. 28.
    Query CC, Bentley RC, Keene JD. A common RNA recognition motif identified within a defined u1 RNA binding domain of the 70 k u1 snrnp protein. Cell. 1989;57:89–101.CrossRefPubMedGoogle Scholar
  29. 29.
    Shamoo Y, Abdul-Manan N, Williams KR. Multiple RNA binding domains (rbds) just don’t add up. Nucleic Acids Res. 1995;23:725–8.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Sanford JR, Ellis J, Caceres JF. Multiple roles of arginine/serine-rich splicing factors in RNA processing. Biochem Soc Trans. 2005;33:443–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Wan L, Kim JK, Pollard VW, Dreyfuss G. Mutational definition of RNA-binding and protein–protein interaction domains of heterogeneous nuclear rnp c1. J Biol Chem. 2001;276:7681–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Scherly D, Dathan NA, Boelens W, van Venrooij WJ, Mattaj IW. The u2b'' rnp motif as a site of protein–protein interaction. EMBO J. 1990;9:3675–81.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Shen H, Green MR. A pathway of sequential arginine–serine-rich domain-splicing signal interactions during mammalian spliceosome assembly. Mol Cell. 2004;16:363–73.CrossRefPubMedGoogle Scholar
  34. 34.
    Ellis JD, Lleres D, Denegri M, Lamond AI, Caceres JF. Spatial mapping of splicing factor complexes involved in exon and intron definition. J Cell Biol. 2008;181:921–34.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Stadler C, Rexhepaj E, Singan VR, Murphy RF, Pepperkok R, Uhlen M, et al. Immunofluorescence and fluorescent-protein tagging show high correlation for protein localization in mammalian cells. Nat Methods. 2013;10:315–23.CrossRefPubMedGoogle Scholar
  36. 36.
    Cazalla D, Newton K, Caceres JF. A novel sr-related protein is required for the second step of pre-mRNA splicing. Mol Cell Biol. 2005;25:2969–80.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yurong Chai
    • 1
    • 2
  • Xinxin Liu
    • 1
  • Liping Dai
    • 1
  • Yang Li
    • 1
  • Mei Liu
    • 1
  • Jian-Ying Zhang
    • 1
  1. 1.Department of Biological SciencesThe University of Texas at El PasoEl PasoUSA
  2. 2.Department of Histology and Embryology, College of Basic MedicineZhengzhou UniversityZhengzhouChina

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