delta-Catenin Increases the Stability of EGFR by Decreasing c-Cbl Interaction and Enhances EGFR/Erk1/2 Signaling in Prostate Cancer
- Authors
- Shrestha, Nensi; Shrestha, Hridaya; Ryu, Taeyong; Kim, Hangun; Simkhada, Shishli; Cho, Young-Chang; Park, So-Yeon; Cho, Sayeon; Lee, Kwang-Youl; Lee, Jae-Hyuk; Kim, Kwonseop
- Issue Date
- Apr-2018
- Publisher
- KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- Keywords
- delta-Catenin; c-Cbl; EGFR; ubiquitination
- Citation
- MOLECULES AND CELLS, v.41, no.4, pp 320 - 330
- Pages
- 11
- Journal Title
- MOLECULES AND CELLS
- Volume
- 41
- Number
- 4
- Start Page
- 320
- End Page
- 330
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/2298
- DOI
- 10.14348/molcells.2018.2292
- ISSN
- 1016-8478
0219-1032
- 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 d-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 d-catenin plays a key role in EGFR stability and downstream signaling. d-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 d-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.
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