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The expression of PEBP4 protein in lung squamous cell carcinoma

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Tumor Biology

Abstract

The phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family. It not only plays a role in the inhibition of the MAPK signaling pathway but also is involved in the inhibition of the JNK pathway that promotes the activation of AKT. Recent research has also shown that overexpression of PEBP4 was related to the development, invasion, and metastasis of a variety of tumors. This study aimed to investigate the correlation between PEBP4 protein expression in lung squamous cell carcinoma tissue and the clinical pathology of lung squamous cell carcinoma. Immunohistochemistry was used to detect PEBP4 expression in lung squamous cell carcinoma tissue and adjacent normal tissue from 61 patients. Western blotting was used to detect changes in the expression of PEBP4 protein between lung squamous cell carcinoma tissue and adjacent normal tissues. The correlation of PEBP4 expression and the occurrence, development, and clinical pathology of lung squamous cell carcinoma was analyzed. Of 61 patients, four patients were PEBP4 negative (−; 6.6%) and 57 patients were positive (+ to +++; 93.4%). Of those positive for PEBP4 expression, 7 patients were weakly positive (+; 11.5%), 21 patients were positive (++; 34.4%), and 29 patients were strongly positive (+++; 47.5%). PEBP4 protein was more highly expressed in lung squamous cell carcinoma tissue than in the adjacent normal lung tissue (p < 0.05). In PEBP4-positive patients, PEBP4 protein expression was significantly greater in those with lymph node metastases than in those without (p < 0.05). PEBP4 expression was significantly lower in patients at early (I and II) stages than in patients at advanced (III and IV) stages (p < 0.05). In less differentiated lung squamous cell carcinomas, PEBP4 protein expression was greater (p < 0.05); however, this was unrelated to the gender, age, or tumor size of the patient (p > 0.05). PEBP4 protein overexpression was associated with the occurrence, invasion, and metastasis of lung squamous cell carcinoma.

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References

  1. Garcia R, Grindlay J, Rath O, et al. Regulation of human myoblast differentiation by PEBP4. EMBO Rep. 2009;10:278–84.

    Article  PubMed  CAS  Google Scholar 

  2. Amaya I, Ratcliffe OJ, Bradley DJ. Expression of CENTRORADIALIS (CEN) and CEN-like genes in tobacco reveals a conserved mechanism controlling phase change in diverse species. Plant Cell. 1999;11:1405–18.

    Article  PubMed  CAS  Google Scholar 

  3. Erttmann KD, Gallin MY. Onchocerca volvulus: identification of cDNAs encoding a putative phosphatidyl-ethanolamine-binding protein and a putative partially processed mRNA precursor. Gene. 1996;174:203–7.

    Article  PubMed  CAS  Google Scholar 

  4. Wilson R, Ainscough R, Anderson K, et al. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994;368:32–8.

    Article  PubMed  CAS  Google Scholar 

  5. Kikuchi R, Kawahigashi H, Ando T, et al. Molecular and functional characterization of PEBP genes in barley reveal the diversification of their roles in flowering. Plant Physiol. 2009;149:1341–53.

    Article  PubMed  CAS  Google Scholar 

  6. Odabaei G, Chatterjee D, Jazirehi AR, et al. Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res. 2004;91:169–200.

    Article  PubMed  CAS  Google Scholar 

  7. Yeung K, Seitz T, Li S, et al. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999;401:173–7.

    Article  PubMed  CAS  Google Scholar 

  8. Corbit KC, Trakul N, Eves EM, et al. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J Biol Chem. 2003;278:13061–8.

    Article  PubMed  CAS  Google Scholar 

  9. Shemon AN, Heil GL, Granovsky AE, et al. Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands. PLoS One. 2010;5:e10479.

    Article  PubMed  Google Scholar 

  10. Al-Mulla F, Bitar MS, Al-Maghrebi M, et al. Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3beta. Cancer Res. 2011;71:1334–43.

    Article  PubMed  CAS  Google Scholar 

  11. Zaravinos A, Chatziioannou M, Lambrou GI, et al. Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res. 2011;17:181–90.

    Article  PubMed  CAS  Google Scholar 

  12. Wang X, Li N, Liu B, et al. A novel human phosphatidylethanolamine-binding protein resists tumor necrosis factor alpha-induced apoptosis by inhibiting mitogen-activated protein kinase pathway activation and phosphatidylethanolamine externalization. J Biol Chem. 2004;279:45855–64.

    Article  PubMed  CAS  Google Scholar 

  13. Qiu J, Xiao J, Han C, et al. Potentiation of tumor necrosis factor-alpha-induced tumor cell apoptosis by a small molecule inhibitor for anti-apoptotic protein hPEBP4. J Biol Chem. 2010;285:12241–7.

    Article  PubMed  CAS  Google Scholar 

  14. Liu H, Qiu J, Li N, et al. Human phosphatidylethanolamine-binding protein 4 promotes transactivation of estrogen receptor alpha (ERalpha) in human cancer cells by inhibiting proteasome-dependent ERalpha degradation via association with Src. J Biol Chem. 2010;285:21934–42.

    Article  PubMed  CAS  Google Scholar 

  15. Zhu XL, Liang L, Ding YQ. Overexpression of FMNL2 is closely related to metastasis of colorectal cancer. Int J Colorectal Dis. 2008;23:1041–7.

    Article  PubMed  Google Scholar 

  16. Vora HH, Patel NA, Rajvik KN, et al. Cytokeratin and vimentin expression in breast cancer. Int J Biol Markers. 2009;24:38–46.

    PubMed  Google Scholar 

  17. Korpanty G, Smyth E, Carney DN. Update on anti-angiogenic therapy in non-small cell lung cancer: are we making progress? J Thorac Dis. 2011;3:19–29.

    CAS  Google Scholar 

  18. Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99.

    CAS  Google Scholar 

  19. Wang X, Li N, Li H, et al. Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest. Clin Cancer Res. 2005;11:7545–53.

    Article  PubMed  CAS  Google Scholar 

  20. Li P, Wang X, Li N, et al. Anti-apoptotic hPEBP4 silencing promotes TRAIL-induced apoptosis of human ovarian cancer cells by activating ERK and JNK pathways. Int J Mol Med. 2006;18:505–10.

    PubMed  CAS  Google Scholar 

  21. Zhang Y, Wang X, Xiang Z, et al. Promotion of cellular migration and apoptosis resistance by a mouse eye-specific phosphatidylethanolamine-binding protein. Int J Mol Med. 2007;19:55–63.

    PubMed  Google Scholar 

  22. Yeung K, Janosch P, McFerran B, et al. Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol. 2000;20:3079–85.

    Article  PubMed  CAS  Google Scholar 

  23. Li H, Wang X, Li N, et al. hPEBP4 resists TRAIL-induced apoptosis of human prostate cancer cells by activating AKT and deactivating ERK1/2 pathways. J Biol Chem. 2007;282:4943–50.

    Article  PubMed  CAS  Google Scholar 

  24. Winn RA, Marek L, Han SY, et al. Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J Biol Chem. 2005;280:19625–34.

    Article  PubMed  CAS  Google Scholar 

  25. Niquet J, Wasterlain CG. Bim, Bad, and Bax: a deadly combination in epileptic seizures. J Clin Invest. 2004;113:960–2.

    PubMed  CAS  Google Scholar 

  26. Jeong SJ, Pise-Masison CA, Radonovich MF, et al. Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cells. Oncogene. 2005;24:6719–28.

    Article  PubMed  CAS  Google Scholar 

  27. Ahmed NN, Grimes HL, Bellacosa A, et al. Transduction of interleukin-2 antiapoptotic and proliferative signals via AKT protein kinase. Proc Natl Acad Sci USA. 1997;94:3627–32.

    Article  PubMed  CAS  Google Scholar 

  28. Lee MY, Ryu JM, Lee SH, et al. Lipid rafts play an important role for maintenance of embryonic stem cell self-renewal. J Lipid Res. 2010;51:2082–9.

    Article  PubMed  CAS  Google Scholar 

  29. Qian Y, Corum L, Meng Q, et al. PI3K induced actin filament remodeling through AKT and p70S6K1: implication of essential role in cell migration. Am J Physiol Cell Physiol. 2004;286:C153–63.

    Article  PubMed  CAS  Google Scholar 

  30. Syed DN, Afaq F, Sarfaraz S, et al. Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol. 2008;231:52–60.

    Article  PubMed  CAS  Google Scholar 

  31. Grille SJ, Bellacosa A, Upson J, et al. The protein kinase AKT induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003;63:2172–8.

    PubMed  CAS  Google Scholar 

  32. Zuo JH, Zhu W, Li MY, et al. Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin. J Cell Biochem. 2011;112:2508–17. doi:10.1002/jcb.23175.

    Article  PubMed  CAS  Google Scholar 

  33. Kim D, Kim S, Koh H, et al. AKT/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 2001;15:1953–62.

    Article  PubMed  CAS  Google Scholar 

  34. Yu HG, Li JY, Yang YN, et al. Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer. Cancer Lett. 2003;195:43–51.

    Article  PubMed  CAS  Google Scholar 

  35. Maroni P, Matteucci E, Luzzati A, et al. Nuclear co-localization and functional interaction of COX-2 and HIF-1alpha characterize bone metastasis of human breast carcinoma. Breast Cancer Res Treat. 2010;129:433–50. doi:10.1007/s10549-010-1240-1.

    Article  PubMed  Google Scholar 

  36. Tahanian E, Sanchez LA, Shiao TC, et al. Flavonoids targeting of IkappaB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells. Drug Des Devel Ther. 2011;5:299–309.

    PubMed  CAS  Google Scholar 

  37. Tammali R, Saxena A, Srivastava SK, et al. Aldose reductase inhibition prevents hypoxia-induced increase in HIF-1{alpha} and VEGF by regulating the 26S proteasome mediated protein degradation in human colon cancer cells. J Biol Chem. 2011;286:24089–100.

    Article  PubMed  CAS  Google Scholar 

  38. Shash E, Peccatori FA, Azim Jr HA. Optimizing the use of epidermal growth factor receptor inhibitors in advanced non-small-lung cancer (NSCLC). J Thorac Dis. 2011;3:57–64.

    CAS  Google Scholar 

  39. Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2:154–9.

    CAS  Google Scholar 

  40. Yang HH, Zhang Q, He JX, Lu WJ. Regulation of calcium signaling in lung cancer. J Thorac Dis. 2010;2:52–6.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, No. 163, Shoushan Rd, Jiangyin, 214400, China

    Gui-Ping Yu, Guo-Qiang Chen, Song Wu, Kai Shen & Yong Ji

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  1. Gui-Ping Yu
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  2. Guo-Qiang Chen
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  4. Kai Shen
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Correspondence to Guo-Qiang Chen.

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Yu, GP., Chen, GQ., Wu, S. et al. The expression of PEBP4 protein in lung squamous cell carcinoma. Tumor Biol. 32, 1257–1263 (2011). https://doi.org/10.1007/s13277-011-0230-1

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  • DOI: https://doi.org/10.1007/s13277-011-0230-1

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