Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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δ-Catenin Increases the Stability of EGFR by Decreasing c-Cbl Interaction and Enhances EGFR/Erk1/2 Signaling in Prostate Cancer

  • Shrestha, Nensi (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Shrestha, Hridaya (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Ryu, Taeyong (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Kim, Hangun (College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Simkhada, Shishli (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Cho, Young-Chang (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Park, So-Yeon (College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Cho, Sayeon (College of Pharmacy, Chung-Ang University) ;
  • Lee, Kwang-Youl (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Lee, Jae-Hyuk (Chonnam National University Hwasun Hospital & Medical School) ;
  • Kim, Kwonseop (College of Pharmacy and Research Institute for Drug Development, Chonnam National University)
  • Received : 2017.11.07
  • Accepted : 2018.01.02
  • Published : 2018.04.30
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Abstract

${\delta}$-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that ${\delta}$-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind ${\delta}$-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that ${\delta}$-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase. c-Cbl monoubiquitinates EGFR and thus facilitates its internalization, followed by lysosomal degradation. We observed that ${\delta}$-catenin plays a key role in EGFR stability and downstream signaling. ${\delta}$-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. This in turn increases the expression of membrane bound EGFR and enhances EGFR/Erk1/2 signaling. Our findings add a new perspective on the role of ${\delta}$-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.

Keywords

References

  1. Anastasiadis, P.Z., and Reynolds, A.B. (2000). The p120 catenin family:complex roles in adhesion, sinalign and cancer. J. Cell Sci. 113, 1319-1334.
  2. Burger, M.J., Tebay, M.A., Keith, P.A., Samaratunga, H.M., Clements, J., Lavin, M.F., and Gardiner, R.A. (2002). Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer. Int. J. Cancer 100, 228-237. https://doi.org/10.1002/ijc.10468
  3. de Melker, A.A., van der Horst, G., Calafat, J., Jansen, H., and Borst, J. (2001). c-Cbl ubiquitinates the EGF receptor at the plasma membrane and remains receptor associated throughout the endocytic route. J. Cell Sci. 114(Pt 11), 2167-2178.
  4. Di Lorenzo, G., Tortora, G., D'Armiento, F.P., De Rosa, G., Staibano, S., Autorino, R., D'Armiento, M., De Laurentiis, M., De Placido, S., Catalano, G., et al. (2002). Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clin. Cancer Res. 8, 3438-3444.
  5. Franovic, A., Gunaratnam, L., Smith, K., Robert, I., Patten, D., and Lee, S. (2007). Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer. Proc. Natl. Acad. Sci. USA 104, 13092-13097. https://doi.org/10.1073/pnas.0702387104
  6. Grovdal, L.M., Stang, E., Sorkin, A., and Madshus, I.H. (2004). Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. Exp. Cell Res. 300, 388-395. https://doi.org/10.1016/j.yexcr.2004.07.003
  7. He, Y.-Y., Huang, J.-L., and Chignell, C.F. (2006). Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization. Oncogene 25, 1521-1531. https://doi.org/10.1038/sj.onc.1209184
  8. He, Y., Ryu, T., Shrestha, N., Yuan, T., Kim, H., Shrestha, H., Cho, Y.C., Seo, Y.W., Song, W.K., and Kim, K. (2016). Interaction of EGFR to ${\delta}$-catenin leads to ${\delta}$-catenin phosphorylation and enhances EGFR signaling. Sci. Rep. 6, 21207. https://doi.org/10.1038/srep21207
  9. Herbst, R.S. (2004). Review of epidermal growth factor receptor biology. Int. J. Rad. Oncol. Biol. Phys. 59, 21-26. https://doi.org/10.1016/j.ijrobp.2003.10.027
  10. Huang, F., Khvorova, A., Marshall, W., and Sorkin, A. (2004). Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. J. Biol. Chem. 279, 16657-16661. https://doi.org/10.1074/jbc.C400046200
  11. Hynes, N.E., and Lane, H.A. (2005). ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer 5, 341-354. https://doi.org/10.1038/nrc1609
  12. Israely, I., Costa, R.M., Xie, C.W., Silva, A.J., Kosik, K.S., and Liu, X. (2004). Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. Curr. Biol. 14, 1657-1663. https://doi.org/10.1016/j.cub.2004.08.065
  13. Joazeiro, C.A., Wing, S.S., Huang, H., Leverson, J.D., Hunter, T., and Liu, Y.C. (1999). The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 286, 309-312. https://doi.org/10.1126/science.286.5438.309
  14. Kim, K., Sirota, A., Chen Yh, Y.H., Jones, S.B., Dudek, R., Lanford, G.W., Thakore, C., and Lu, Q. (2002). Dendrite-like process formation and cytoskeletal remodeling regulated by delta-catenin expression. Exp. Cell Res. 275, 171-184. https://doi.org/10.1006/excr.2002.5503
  15. Kim, H., Ki, H., Park, H.-S., and Kim, K. (2005). Presenilin-1 D257A and D385A mutants fail to cleave Notch in their endoproteolyzed forms, but only presenilin-1 D385A mutant can restore its gammasecretase activity with the compensatory overexpression of normal Cterminal fragment. J. Biol. Chem. 280, 22462-22472. https://doi.org/10.1074/jbc.M502769200
  16. Kim, H., Han, J.R., Park, J., Oh, M., James, S.E., Chang, S., Lu, Q., Lee, K.Y., Ki, H., Song, W.J., et al. (2008). Delta-Catenin-induced dendritic morphogenesis: An essential role of p190RhoGEF interaction through AKT1-mediated phosphorylation. J. Biol. Chem. 283, 977-987. https://doi.org/10.1074/jbc.M707158200
  17. Kim, H., He, Y., Yang, I., Zeng, Y., Kim, Y., Seo, Y.W., Murnane, M.J., Jung, C., Lee, J.H., Min, J.J., et al. (2012). ${\delta}$-Catenin promotes Ecadherin processing and activates ${\delta}$-catenin-mediated signaling: Implications on human prostate cancer progression. Biochimi. Biophys. Acta 1822, 509-521. https://doi.org/10.1016/j.bbadis.2011.12.015
  18. Kirisits, A., Pils, D., and Krainer, M. (2007). Epidermal growth factor receptor degradation: An alternative view of oncogenic pathways. Int. J. Biochem. Cell Biol. 39, 2173-2182. https://doi.org/10.1016/j.biocel.2007.07.012
  19. Levkowitz, G., Waterman, H., Zamir, E., Kam, Z., Oved, S., Langdon, W. Y., Beguinot, L., Geiger, B., and Yarden, Y. (1998). c-Cb1/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. 12, 3663-3674. https://doi.org/10.1101/gad.12.23.3663
  20. Levkowitz, G., Waterman, H., Ettenberg, S.A., Katz, M., Tsygankov, A.Y., Alroy, I., Lavi, S., Iwai, K., Reiss, Y., Ciechanover, A,. et al. (1999). Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4, 1029-1040. https://doi.org/10.1016/S1097-2765(00)80231-2
  21. Longva, K.E., Blystad, F.D., Stang, E., Larsen, A.M., Johannessen, L.E., and Madshus, I.H. (2002). Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies. J. Cell Biol. 156, 843-854. https://doi.org/10.1083/jcb.200106056
  22. Lu, Q., Dobbs, L.J., Gregory, C.W., Lanford, G.W., Revelo, M.P., Shappell, S., and Chen, Y.H. (2005). Increased expression of deltacatenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer. Hum. Pathol. 36, 1037-1048. https://doi.org/10.1016/j.humpath.2005.07.012
  23. Lu, Q., Zhang, J., Allison, R., Gay, H., Yang, W.-X., Bhowmick, N.A., Frelix, G., Shappell, S., and Chen, Y.H. (2009). Identification of extracellular delta-catenin accumulation for prostate cancer detection. The Prostate 69, 411-418. https://doi.org/10.1002/pros.20902
  24. Lupher, M.L., Andoniou, C.E., Bonita, D., Miyake, S., and Band, H. (1998). Molecules in focus: The c-Cbl oncoprotein. Int. J. Biochem. Cell Biol. 30, 439-444. https://doi.org/10.1016/S1357-2725(97)00075-7
  25. Nguyen, T.T., Yoon, S., Yang, Y., Lee, H. Bin, Oh, S., Jeong, M.H., Kim, J.J., Yee, S.T., Crisan, F., Moon, C., et al. (2014). Lichen secondary metabolites in Flavocetraria cucullata Exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials. PLoS One 9, e111575. https://doi.org/10.1371/journal.pone.0111575
  26. Normanno, N., De Luca, A., Bianco, C., Strizzi, L., Mancino, M., Maiello, M.R., Carotenuto, A., De Feo, G., Caponigro, F., and Salomon, D.S. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 266, 2-16.
  27. Prenzel, N., Fischer, O.M., Streit, S., Hart, S., and Ullrich, A. (2001). The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr. Relat. Cancer 8, 11-31. https://doi.org/10.1677/erc.0.0080011
  28. Ravid, T., Heidinger, J.M., Gee, P., Khan, E.M., and Goldkorn, T. (2004). c-Cbl-mediated ubiquitinylation is required for epidermal growth factor receptor exit from the early endosomes. J. Biol. Chem. 279, 37153-37162. https://doi.org/10.1074/jbc.M403210200
  29. Repetto, E., Yoon, I.S., Zheng, H., and Kang, D.E. (2007). Presenilin 1 regulates epidermal growth factor receptor turnover and signaling in the endosomal-lysosomal pathway. J. Biol. Chem. 282, 31504-31516. https://doi.org/10.1074/jbc.M704273200
  30. Rocher-Ros, V., Marco, S., Mao, J.-H., Gines, S., Metzger, D., Chambon, P., Balmain, A., Saura, C. (2010). Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene 29, 2950-2961. https://doi.org/10.1038/onc.2010.57
  31. Roepstorff, K., Grandal, M.V., Henriksen, L., Knudsen, S.L.J., Lerdrup, M., Grovdal, L., Willumsen, B.M., and Van Deurs, B. (2009). Differential effects of EGFR ligands on endocytic sorting of the receptor. Traffic 10, 1115-1127. https://doi.org/10.1111/j.1600-0854.2009.00943.x
  32. Scaltriti, M., and Baselga, J. (2006). The epidermal growth factor receptor pathway : a model for targeted therapy. Clin. Cancer Res. 12, 5268-5272. https://doi.org/10.1158/1078-0432.CCR-05-1554
  33. Thien, C.B.F., and Langdon, W.Y. (2005). c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Biochem. J. 391, 153-166. https://doi.org/10.1042/BJ20050892
  34. Tomas, A., Futter, C.E., and Eden, E.R. (2014). EGF receptor trafficking: consequences for signaling and cancer. Trends Cell Biol. 24, 26-34. https://doi.org/10.1016/j.tcb.2013.11.002
  35. Yang, I., Chang, O., Lu, Q., and Kim, K. (2010). ${\delta}$-catenin affects the localization and stability of p120-Catenin by competitively interacting with E-cadherin. Mol. Cells 29, 233-237. https://doi.org/10.1007/s10059-010-0030-2
  36. Yarden, Y. (2001). The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 37, S3-S8.
  37. Yarden, Y., and Sliwkowski, M.X. (2001). Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol. 2, 127-137. https://doi.org/10.1038/35052073
  38. Yokouchi, M., Kondo, T., Houghton, A., Bartkiewicz, M., Horne, W. C., Zhang, H., Yoshimura, A., and Baron, R. (1999). Ligand-induced Uubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING Finger and UbcH7. J. Biol. Chem. 274, 31707-31712. https://doi.org/10.1074/jbc.274.44.31707
  39. Zeng, Y., Abdallah, A., Lu, J.-P., Wang, T., Chen, Y.-H., Terrian, D.M., Kim, K., and Lu, Q. (2009). ${\delta}$-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles. Mol. Cancer 8, 19. https://doi.org/10.1186/1476-4598-8-19
  40. Zhou, J., Liyanage, U., Medina, M., Ho, C., Simmons, A.D., Lovett, M., and Kosik, K.S. (1997). Presenilin 1 interaction in the brain with a novel member of the Armadillo family. Neuroreport 8, 2085-2090. https://doi.org/10.1097/00001756-199705260-00054
  41. Zhuang, S., Ouedraogo, G.D., and Kochevar, I.E. (2003). Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases. Oncogene 22, 4413-4424. https://doi.org/10.1038/sj.onc.1206604

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