Tumor Biology

, Volume 37, Issue 4, pp 5075–5087 | Cite as

CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors

  • Wei Chen
  • Zhen Hu
  • Xi-zhao Li
  • Jun-liang Li
  • Xin-Ke Xu
  • Hai-gang Li
  • Yeqing Liu
  • Bai-hui Liu
  • Wei-hua Jia
  • Fang-cheng Li
Original Article


Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4’s function and mechanisms. Co-immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1–11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability, clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and β-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors.


Astrocytic tumor CPEB4 Vimentin Prognosis 



This study was supported by the National Natural Science Foundation of China (No. 81272774, No. 30500528/C03030307, No. 81572497) and the Guangdong Province Natural Science Foundation (No. 9151008901000114).

Conflicts of interest



  1. 1.
    Gandini NA, Fermento ME, Salomon DG, Obiol DJ, Andres NC, Zenklusen JC, et al. Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma. Tumor Biol. 2014;35(3):2803–15.CrossRefGoogle Scholar
  2. 2.
    Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol. 2012;14 Suppl 5:v1–49.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Smoll NR, Schaller K, Gautschi OP. Long-term survival of patients with glioblastoma multiforme (GBM). J Clin Neurosci. 2013;20(5):670–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Towia A, Libermann HRN, Nissim R, Richard K, Irit L, Hermona S, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985;313:144–7.CrossRefGoogle Scholar
  5. 5.
    Yin SMEV, Gliomas Á, Apoptosis ÁSÁ, Cell Á. p53 Pathway alteration in brain tumors. Humana Press. 2009.Google Scholar
  6. 6.
    Koul D, Shen R, Shishodia S, Takada Y, Bhat KP, Reddy SA. PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Mol Cell Biochem. 2007;300(1–2):77–87.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science. 2009;324(5924):261–5.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yang M, Yuan Y, Zhang H, Yan M, Wang S, Feng F, et al. Prognostic significance of CD147 in patients with glioblastoma. J Neurooncol. 2013;115(1):19–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Lin W, Li XM, Zhang J, Huang Y, Wang J, Jiang XF, et al. Increased expression of the 58-kD microspherule protein (MSP58) is correlated with poor prognosis in glioma patients. Med Oncol. 2013;30(4):677.CrossRefPubMedGoogle Scholar
  10. 10.
    Nuno M, Birch K, Mukherjee D, Sarmiento JM, Black KL, Patil CG. Survival and prognostic factors of anaplastic gliomas. Neurosurgery. 2013;73(3):458–65.CrossRefPubMedGoogle Scholar
  11. 11.
    Shibahara I, Sonoda Y, Saito R, Kanamori M, Yamashita Y, Kumabe T, et al. The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence. Neuro Oncol. 2013;15(9):1151–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mendez R, Richter JD. Translational control by CPEB: a means to the end. Nat Rev Mol Cell Biol. 2001;2(7):521–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Richter JD. CPEB: a life in translation. Trends Biochem Sci. 2007;32(6):279–85.CrossRefPubMedGoogle Scholar
  14. 14.
    Burns DM, Richter JD. CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation. Genes Dev 2008;2 2(24): 3449–3460.Google Scholar
  15. 15.
    Eliscovich C, Peset I, Vernos I, Mendez R. Spindle-localized CPE-mediated translation controls meiotic chromosome segregation. Nat Cell Biol. 2008;10(7):858–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Livingstone M, Atas E, Meller A, Sonenberg N. Mechanisms governing the control of mRNA translation. Phys Biol. 2010;7(2):021001.CrossRefPubMedGoogle Scholar
  17. 17.
    Pique M, Lopez JM, Foissac S, Guigo R, Mendez R. A combinatorial code for CPE-mediated translational control. Cell. 2008;132(3):434–48.CrossRefPubMedGoogle Scholar
  18. 18.
    Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998;4(7):844–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kan MC, Oruganty-Das A, Cooper-Morgan A, Jin G, Swanger SA, Bassell GJ, et al. CPEB4 is a cell survival protein retained in the nucleus upon ischemia or endoplasmic reticulum calcium depletion. Mol Cell Biol. 2010;30(24):5658–71.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Novoa I, Gallego J, Ferreira PG, Mendez R. Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control. Nat Cell Biol. 2010;12(5):447–56.CrossRefPubMedGoogle Scholar
  21. 21.
    Ortiz-Zapater E, Pineda D, Martinez-Bosch N, Fernandez-Miranda G, Iglesias M, Alameda F, et al. Key contribution of CPEB4-mediated translational control to cancer progression. Nat Med. 2012;18(1):83–90.CrossRefGoogle Scholar
  22. 22.
    Xu H, Liu B. CPEB4 is a candidate biomarker for defining metastatic cancers and directing personalized therapies. Med Hypotheses. 2013;81(5):875–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Robert L. Camp MD-FaDLR. X-Tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Re 10: 7252–7259.Google Scholar
  24. 24.
    Paciucci R, Tora M, Diaz VM, Real FX. The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Oncogene. 1998;16(5):625–33.CrossRefPubMedGoogle Scholar
  25. 25.
    Blasi F, Sidenius N. The urokinase receptor: focused cell surface proteolysis, cell adhesion and signaling. FEBS Lett. 2010;584(9):1923–30.CrossRefPubMedGoogle Scholar
  26. 26.
    Saaf AM, Halbleib JM, Chen X, Yuen ST, Leung SY, Nelson WJ, et al. Parallels between global transcriptional programs of polarizing Caco-2 intestinal epithelial cells in vitro and gene expression programs in normal colon and colon cancer. Mol Biol Cell. 2007;18(11):4245–60.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136(4):731–45.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gandin V, Miluzio A, Barbieri AM, Beugnet A, Kiyokawa H, Marchisio PC, et al. Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation. Nature. 2008;455(7213):684–8.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Tsai LY, Chang YW, Lin PY, Chou HJ, Liu TJ, Lee PT, et al. CPEB4 knockout mice exhibit normal hippocampus-related synaptic plasticity and memory. PLoS one. 2013;8(12):e84978.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Theis M, Si K, Kandel ER. Two previously undescribed members of the mouse CPEB family of genes and their inducible expression in the principal cell layers of the hippocampus. Proc Natl Acad Sci U S A. 2003;100(16):9602–7.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Wei Chen
    • 1
    • 2
    • 3
  • Zhen Hu
    • 1
  • Xi-zhao Li
    • 3
  • Jun-liang Li
    • 1
    • 2
  • Xin-Ke Xu
    • 2
  • Hai-gang Li
    • 4
  • Yeqing Liu
    • 4
  • Bai-hui Liu
    • 5
  • Wei-hua Jia
    • 3
  • Fang-cheng Li
    • 1
    • 2
  1. 1.Department of Neurosurgery, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of NeurosurgeryGuangzhou Women and Children’s Medical CenterGuangzhouChina
  3. 3.State Key Laboratory of Oncology in South ChinaSun Yat-Sen University Cancer CenterGuangzhouChina
  4. 4.Department of Pathology, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
  5. 5.Department of General SurgeryThe Second Affiliated Hospital of GuangDong Pharmaceutical UniversityGuangzhouChina

Personalised recommendations