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The Role of CYLD in Blocking Oncogenic Cell Signaling in Melanoma

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DOI: 10.4236/jct.2013.46A1005    3,195 Downloads   4,702 Views   Citations

ABSTRACT

Dysregulation of components of the ubiqutin system has been linked to many diseases including melanoma. This is vital since the post-translational modification of different proteins via direct ubiquitin attachment is an important process for various cellular processes. CYLD is a tumor suppressor gene and deubiquitinating enzyme, which can remove polyubiquitin chains from their specific substrate and interfere with different signaling pathways. CYLD is frequently downregulated or even lost in melanoma cell lines or tissues compared to melanocytes. Down-regulation of CYLD leads to sustained oncogenic signaling that promotes melanoma progression and metastasis. In this review, we summarize the recent insights into the mechanisms which are responsible for the down-regulation of CYLD levels in melanoma and the signaling interactions of the CYLD gene product in melanoma. We argue that these recent insights into CYLD function invite the development of novel molecular strategies for melanoma prevention and treatment.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

H. Ke and R. Massoumi, "The Role of CYLD in Blocking Oncogenic Cell Signaling in Melanoma," Journal of Cancer Therapy, Vol. 4 No. 6A, 2013, pp. 32-37. doi: 10.4236/jct.2013.46A1005.

References

[1] A. M. Weissman, “Themes and Variations on Ubiquitylation,” Nature Reviews Molecular Cell Biology, Vol. 2, No. 3, 2001, pp. 169-178. doi:10.1038/35056563
[2] C. M. Pickart, “Mechanisms Underlying Ubiquitination,” Annual Review of Biochemistry, Vol. 70, 2001, pp. 503-533. doi:10.1146/annurev.biochem.70.1.503
[3] R. Massoumi, “Ubiquitin Chain Cleavage: CYLD at Work,” Trends in Biochemical Science, Vol. 35, No. 7, 2010, pp. 392-399. doi:10.1016/j.tibs.2010.02.007
[4] S. M. B. Nijman, et al., “A Genomic and Functional Inventory of Deubiquitinating Enzymes,” Cell, Vol. 123, No. 5, 2005, pp. 773-786. doi:10.1016/j.cell.2005.11.007
[5] C. Luise, et al., “An Atlas of Altered Expression of Deubiquitinating Enzymes in Human Cancer,” PLoS One, Vol. 6, No. 1, 2011, Article ID: e15891. doi:10.1371/journal.pone.0015891
[6] X. Zhao, et al., “Regulation of MITF Stability by the USP13 Deubiquitinase,” Nature Communications, Vol. 2, 2011, p. 414. doi:10.1038/ncomms1421
[7] T. Wiesner, et al., “Germline Mutations in BAP1 Predispose to Melanocytic Tumors,” Nature Genetics, Vol. 43, No. 10, 2011, pp. 1018-1021. doi:10.1038/ng.910
[8] J. R. Testa, et al., “Germline BAP1 Mutations Predispose to Malignant Mesothelioma,” Nature Genetics, Vol. 43, No. 10, 2011, pp. 1022-1025. doi:10.1038/ng.912
[9] J. Wulfanger, et al., “Heterogeneous Expression and Functional Relevance of the Ubiquitin Carboxyl-Terminal Hydrolase L1 in Melanoma,” International Journal of Cancer, 2013. doi:10.1002/ijc.28278
[10] P. J. Biggs, et al., “Familial Cylindromatosis (Turban Tumor Syndrome) Gene Localized to Chromosome 16Q12-Q13—Evidence for Its Role as a Tumor-Suppressor Gene,” Nature Genetics, Vol. 11, No. 4, 1995, pp. 441-443. doi:10.1038/ng1295-441
[11] G. R. Bignell, et al., “Identification of the Familial Cylindromatosis Tumor-Suppressor Gene,” Nature Genetics, Vol. 25, No. 2, 2000, pp. 160-165. doi:10.1038/76006
[12] D. Komander, et al., “The Structure of the CYLD USP Domain Explains Its Specificity for Lys63-Linked Polyubiquitin and Reveals a B Box Module,” Molecular Cell, Vol. 29, No. 4, 2008, pp. 451-464. doi:10.1016/j.molcel.2007.12.018
[13] R. Massoumi, “CYLD: A Deubiquitination Enzyme with Multiple Roles in Cancer,” Future Oncology, Vol. 7, No. 2, 2011, pp. 285-297. doi:10.2217/fon.10.187
[14] R. Massoumi and R. Paus, “Cylindromatosis and the CYLD Gene: New Lessons on the Molecular Principles of Epithelial Growth Control,” Bioessays, Vol. 29, No. 12, 2007, pp. 1203-1214. doi:10.1002/bies.20677
[15] K. C. Masoumi, G. Shaw-Hallgren and R. Massoumi, “Tumor Suppressor Function of CYLD in Non-Melanoma Skin Cancer,” Journal of Skin Cancer, Vol. 2011, 2011, Article ID: 614097. doi:10.1155/2011/614097
[16] R. Massoumi, et al., “Down-Regulation of CYLD Expression by Snail Promotes Tumor Progression in Malignant Melanoma,” Journal of Experimental Medicine, Vol. 206, No. 1, 2009, pp. 221-232. doi:10.1084/jem.20082044
[17] H. Ke, et al., “CYLD Inhibits Melanoma Growth and Progression through Suppression of the JNK/AP-1 and Beta1-Integrin Signaling Pathways,” Journal of Invest Dermatology, Vol. 133, No. 1, 2013, pp. 221-229. doi:10.1038/jid.2012.253
[18] Y. Ishikawa, et al., “Down-Regulation of Cylindromatosis Gene, CYLD, Confers a Growth Advantage on Malignant Melanoma Cells While Negatively Regulating Their Migration Activity,” International Journal of Oncology, Vol. 41, No. 1, 2012, pp. 53-60.
[19] P. C. Cogswell, et al., “Selective Activation of NF-Kappa B Subunits in Human Breast Cancer: Potential Roles for NF-Kappa B2/p52 and for Bcl-3,” Oncogene, Vol. 19, No. 9, 2000, pp. 1123-1131. doi:10.1038/sj.onc.1203412
[20] S. G. Park, et al., “Up-Regulation of Cyclin D1 by HBx Is Mediated by NF-KappaB2/BCL3 Complex through KappaB Site of Cyclin D1 Promoter,” Journal of Biological Chemistry, Vol. 281, No. 42, 2006, pp. 31770-31777. doi:10.1074/jbc.M603194200
[21] R. Massoumi, et al., “CYLD Inhibits Tumor Cell Proliferation by Blocking Bcl-3-dependent NF-Kappa B Signaling,” Cell, Vol. 125, No. 4, 2006, pp. 665-677. doi:10.1016/j.cell.2006.03.041
[22] D. G. Uffort, E. A. Grimm and J. A. Ellerhorst, “NF-Kappa B Mediates Mitogen-Activated Protein Kinase PathWay-Dependent iNOS Expression in Human Melanoma,” Journal of Investigative Dermatology, Vol. 129, No. 1, 2009, pp. 148-154. doi:10.1038/jid.2008.205
[23] Y. Zhang, et al., “HDAC-6 Interacts with and Deacetylates Tubulin and Microtubules in Vivo,” EMBO Journal, Vol. 22, No. 5, 2003, pp. 1168-1179. doi:10.1093/emboj/cdg115
[24] K. Tsunoda, et al., “Nucleus Accumbens-Associated 1 Contributes to Cortactin Deacetylation and Augments the Migration of Melanoma Cells,” Journal of Invest Dermatology, Vol. 131, No. 8, 2011, pp. 1710-1719. doi:10.1038/jid.2011.110
[25] J. A. Bergman, et al., “Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth,” Journal of Medical Chemistry, Vol. 55, No. 22, 2012, pp. 9891-9899. doi:10.1021/jm301098e
[26] P. Pinon and B. Wehrle-Haller, “Integrins: Versatile Receptors Controlling Melanocyte Adhesion, Migration and Proliferation,” Pigment Cell Melanoma Research, Vol. 24, No. 2, 2011, pp. 282-294. doi:10.1111/j.1755-148X.2010.00806.x
[27] A. S. Harney, T. J. Meade and C. LaBonne, “Targeted Inactivation of Snail Family EMT Regulatory Factors by a Co(III)-Ebox Conjugate,” PLoS One, Vol. 7, No. 2, 2012, Article ID: e32318. doi:10.1371/journal.pone.0032318
[28] G. M. Boyle, A. C. Martyn and P. G. Parsons, “Histone Deacetylase Inhibitors and Malignant Melanoma,” Pigment Cell Research, Vol. 18, No. 3, 2005, pp. 160-166. doi:10.1111/j.1600-0749.2005.00228.x
[29] M. Yoshida, et al., “Histone Deacetylase as a New Target for Cancer Chemotherapy,” Cancer Chemotherapy Pharmacology, Vol. 48, No. S1, 2001, p. S20-S26. doi:10.1007/s002800100300
[30] S. M. Albelda, et al., “Integrin Distribution in Malignant Melanoma: Association of the Beta 3 Subunit with Tumor Progression,” Cancer Research, Vol. 50, No. 20, 1990, pp. 6757-6764.
[31] E. H. Danen, et al., “Integrins and Melanoma Progression,” Recent Results Cancer Research, Vol. 128, 1993, pp. 119-132. doi:10.1007/978-3-642-84881-0_9

  
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