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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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P42 Ebp1 functions as a tumor suppressor in non-small cell lung cancer

  • Ko, Hyo Rim (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Nguyen, Truong L.X. (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Kim, Chung Kwon (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Park, Youngbin (Department of Biology, Johns Hopkins University) ;
  • Lee, Kyung-Hoon (Anatomy, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Ahn, Jee-Yin (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine)
  • Received : 2014.06.17
  • Accepted : 2014.07.02
  • Published : 2015.03.31
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Abstract

Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling.

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References

  1. Liu Z, Ahn JY, Liu X and Ye K (2006) Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc Natl Acad Sci U S A 103, 10917-10922 https://doi.org/10.1073/pnas.0602923103
  2. Ahn JY, Liu X, Liu Z et al (2006) Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase. EMBO J 25, 2083-2095 https://doi.org/10.1038/sj.emboj.7601111
  3. Kim CK, Nguyen TL, Joo KM et al (2010) Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors. Cancer Res 70, 9730-9741 https://doi.org/10.1158/0008-5472.CAN-10-1882
  4. Kim CK, Lee SB, Nguyen TL et al (2012) Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Aktdependent HDM2 stabilization and nuclear localization. Exp Cell Res 318, 136-143 https://doi.org/10.1016/j.yexcr.2011.08.013
  5. Ou K, Kesuma D, Ganesan K et al (2006) Quantitative profiling of drug-associated proteomic alterations by combined 2-nitrobenzenesulfenyl chloride (NBS) isotope labeling and 2DE/MS identification. J Proteome Res 5, 2194-2206 https://doi.org/10.1021/pr060115n
  6. Gannon PO, Koumakpayi IH, Le Page C, Karakiewicz PI, Mes-Masson AM and Saad F (2008) Ebp1 expression in benign and malignant prostate. Cancer Cell Int 8, 18-2867-8-18 https://doi.org/10.1186/1475-2867-8-18
  7. Xia X, Cheng A, Lessor T, Zhang Y and Hamburger AW (2001) Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation. J Cell Physiol 187, 209-217 https://doi.org/10.1002/jcp.1075
  8. Zhang Y, Woodford N, Xia X and Hamburger AW (2003) Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nucleic Acids Res 31, 2168-2177 https://doi.org/10.1093/nar/gkg318
  9. Yu Y, Chen W, Zhang Y, Hamburger AW, Pan H and Zhang Z (2007) Suppression of salivary adenoid cystic carcinoma growth and metastasis by ErbB3 binding protein Ebp1 gene transfer. Int J Cancer 120, 1909-1913 https://doi.org/10.1002/ijc.22541
  10. Zhang Y, Wang XW, Jelovac D et al (2005) The ErbB3- binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells. Proc Natl Acad Sci U S A 102, 9890-9895 https://doi.org/10.1073/pnas.0503829102
  11. Liu Z, Oh SM, Okada M et al (2009) Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor. Mol Biol Cell 20, 757-768 https://doi.org/10.1091/mbc.E08-09-0983
  12. Hoffman PC, Mauer AM and Vokes EE (2000) Lung cancer. Lancet 355, 479-485 https://doi.org/10.1016/S0140-6736(00)82038-3
  13. Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24, 4539-4544 https://doi.org/10.1200/JCO.2005.04.4859
  14. Engelman JA and Cantley LC (2006) The role of the ErbB family members in non-small cell lung cancers sensitive to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 12, 4372s-4376s https://doi.org/10.1158/1078-0432.CCR-06-0795
  15. Laskin JJ and Sandler AB (2004) Epidermal growth factor receptor: a promising target in solid tumours. Cancer Treat Rev 30, 1-17 https://doi.org/10.1016/j.ctrv.2003.10.002
  16. Okoh V, Young GD, Winokur TS and Garver RI Jr (2004) A novel assay for the quantification of invasion from raft cultures of lung carcinomas. Clin Exp Metastasis 21, 1-6 https://doi.org/10.1023/B:CLIN.0000017159.12425.c9
  17. Donev IS, Wang W, Yamada T et al (2011) Transient PI3K inhibition induces apoptosis and overcomes HGF-mediated resistance to EGFR-TKIs in EGFR mutant lung cancer. Clin Cancer Res 17, 2260-2269 https://doi.org/10.1158/1078-0432.CCR-10-1993
  18. Monie TP, Perrin AJ, Birtley JR et al (2007) Structural insights into the transcriptional and translational roles of Ebp1. EMBO J 26, 3936-3944 https://doi.org/10.1038/sj.emboj.7601817
  19. Ahn JY, Rong R, Kroll TG, Van Meir EG, Snyder SH and Ye K (2004) PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt activity and mediates cellular invasion. J Biol Chem 279, 16441-16451 https://doi.org/10.1074/jbc.M312175200
  20. Xie H, Hu J, Pan H, Lou Y, Lv P and Chen Y (2014) Adenovirus vector-mediated FAM176A overexpression induces cell death in human H1299 non-small cell lung cancer cells. BMB Rep 47, 104-109 https://doi.org/10.5483/BMBRep.2014.47.2.090
  21. Bai M, Ni J, Shen S, Huang Q, Wu J, Le Y and Yu L (2014) Aurora-A kinase-inactive mutants disrupt the interaction with Ajuba and cause defects in mitotic spindle formation and G2/M phase arrest in HeLa cells. BMB Rep 47, 631-636 https://doi.org/10.5483/BMBRep.2014.47.11.250

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