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?-Catenin Increases the Stability of EGFR by Decreasing c-Cbl Interaction and Enhances EGFR/Erk1/2 Signaling in Prostate Cancer.


ABSTRACT: ?-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 ?-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind ?-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that ?-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 ?-catenin plays a key role in EGFR stability and downstream signaling. ?-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 ?-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.

SUBMITTER: Shrestha N 

PROVIDER: S-EPMC5935102 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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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 N   Shrestha Hridaya H   Ryu Taeyong T   Kim Hangun H   Simkhada Shishli S   Cho Young-Chang YC   Park So-Yeon SY   Cho Sayeon S   Lee Kwang-Youl KY   Lee Jae-Hyuk JH   Kim Kwonseop K  

Molecules and cells 20180405 4


δ-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 δ-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind δ-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that δ-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-cas  ...[more]

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