Over-expression of 14-3-3zeta is an Early Event in Oral Cancer

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2007 Sep 4

PMID 17764575

Citations 31

Authors

Ajay Matta

Sudhir Bahadur

Ritu Duggal

Siddhartha D Gupta

Ranju Ralhan

Affiliations

Soon will be listed here.

Abstract

Background: The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3zeta mRNA in oral squamous cell carcinoma (OSCC) by differential display.

Methods: The clinical relevance of 14-3-3zeta protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFkappaB, beta-catenin and Bcl-2.

Results: Intense immunostaining of 14-3-3zeta protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3zeta protein from normal mucosa to OPLs to OSCCs (ptrend < 0.001). Significant increase in expression of 14-3-3zeta protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3zeta protein binds to NFkappaB, beta-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells.

Conclusion: Our findings suggest that over-expression of 14-3-3zeta is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3zeta may serve as an important molecular target for designing novel therapy for oral cancer.

Citing Articles

Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma.

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14-3-3ζ targeting induced senescence in Hep-2 laryngeal cancer cell through deneddylation of Cullin1 in the Skp1-Cullin-F-box protein complex.

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Qin J, Wang S, Wang P, Wang X, Ye H, Song C J Cancer Res Clin Oncol. 2019; 145(5):1253-1262.

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References

Rena G, Prescott A, Guo S, Cohen P, Unterman T . Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting. Biochem J. 2001; 354(Pt 3):605-12. PMC: 1221692. DOI: 10.1042/0264-6021:3540605. View

Tzivion G, Avruch J . 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation. J Biol Chem. 2001; 277(5):3061-4. DOI: 10.1074/jbc.R100059200. View

Hermeking H, Benzinger A . 14-3-3 proteins in cell cycle regulation. Semin Cancer Biol. 2006; 16(3):183-92. DOI: 10.1016/j.semcancer.2006.03.002. View

Tzivion G, Gupta V, Kaplun L, Balan V . 14-3-3 proteins as potential oncogenes. Semin Cancer Biol. 2006; 16(3):203-13. DOI: 10.1016/j.semcancer.2006.03.004. View

Lau J, Wu C, Muslin A . Differential role of 14-3-3 family members in Xenopus development. Dev Dyn. 2006; 235(7):1761-76. DOI: 10.1002/dvdy.20816. View

Shikano S, Coblitz B, Wu M, Li M . 14-3-3 proteins: regulation of endoplasmic reticulum localization and surface expression of membrane proteins. Trends Cell Biol. 2006; 16(7):370-5. DOI: 10.1016/j.tcb.2006.05.006. View

Aguilera C, Fernandez-Majada V, Ingles-Esteve J, Rodilla V, Bigas A, Espinosa L . Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins. J Cell Sci. 2006; 119(Pt 17):3695-704. DOI: 10.1242/jcs.03086. View

Sharma C, Kaur J, Shishodia S, Aggarwal B, Ralhan R . Curcumin down regulates smokeless tobacco-induced NF-kappaB activation and COX-2 expression in human oral premalignant and cancer cells. Toxicology. 2006; 228(1):1-15. DOI: 10.1016/j.tox.2006.07.027. View

Henson E, Gibson S . Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: implications for cancer therapy. Cell Signal. 2006; 18(12):2089-97. DOI: 10.1016/j.cellsig.2006.05.015. View

10.

Li J, Tewari M, Vidal M, Lee S . The 14-3-3 protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev Biol. 2006; 301(1):82-91. PMC: 1963419. DOI: 10.1016/j.ydbio.2006.10.013. View

11.

Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H . Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem. 2007; 282(15):11221-9. PMC: 1850976. DOI: 10.1074/jbc.M611871200. View

12.

Sawhney M, Rohatgi N, Kaur J, Shishodia S, Sethi G, Gupta S . Expression of NF-kappaB parallels COX-2 expression in oral precancer and cancer: association with smokeless tobacco. Int J Cancer. 2007; 120(12):2545-56. DOI: 10.1002/ijc.22657. View

13.

Hermeking H . 14-3-3 proteins and cancer biology. Semin Cancer Biol. 2006; 16(3):161. DOI: 10.1016/j.semcancer.2006.03.001. View

14.

Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C, Birchmeier W . Requirement for beta-catenin in anterior-posterior axis formation in mice. J Cell Biol. 2000; 148(3):567-78. PMC: 2174807. DOI: 10.1083/jcb.148.3.567. View

15.

van Zeijl M, Testerink C, Kijne J, Wang M . Subcellular differences in post-translational modification of barley 14-3-3 proteins. FEBS Lett. 2000; 473(3):292-6. DOI: 10.1016/s0014-5793(00)01545-3. View

16.

Cahill C, Tzivion G, Nasrin N, Ogg S, Dore J, Ruvkun G . Phosphatidylinositol 3-kinase signaling inhibits DAF-16 DNA binding and function via 14-3-3-dependent and 14-3-3-independent pathways. J Biol Chem. 2001; 276(16):13402-10. DOI: 10.1074/jbc.M010042200. View

17.

van Hemert M, Steensma H, van Heusden G . 14-3-3 proteins: key regulators of cell division, signalling and apoptosis. Bioessays. 2001; 23(10):936-46. DOI: 10.1002/bies.1134. View

18.

Tzivion G, Shen Y, Zhu J . 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene. 2001; 20(44):6331-8. DOI: 10.1038/sj.onc.1204777. View

19.

Sharma R, Samantaray S, Shukla N, Ralhan R . Transcriptional gene expression profile of human esophageal squamous cell carcinoma. Genomics. 2003; 81(5):481-8. DOI: 10.1016/s0888-7543(03)00023-5. View

20.

Powell D, Rane M, Joughin B, Kalmukova R, Hong J, Tidor B . Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated protein kinase 2 substrate: role in dimer formation and ligand binding. Mol Cell Biol. 2003; 23(15):5376-87. PMC: 165733. DOI: 10.1128/MCB.23.15.5376-5387.2003. View