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Erbin interacts with c‐Cbl and promotes tumourigenesis and tumour growth in colorectal cancer by preventing c‐Cbl‐mediated ubiquitination and down‐regulation of EGFR
Author(s) -
Yao Su,
Zheng Ping,
Wu Hua,
Song LiMing,
Ying XiaoFang,
Xing Cheng,
Li Ying,
Xiao ZhengQuan,
Zhou XingNi,
Shen Tong,
Chen Lin,
Liu YuHong,
Lai MaoDe,
Mei Lin,
Gao TianMing,
Li JianMing
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4502
Subject(s) - pdz domain , azoxymethane , cancer research , epidermal growth factor receptor , colorectal cancer , ubiquitin ligase , cancer , ubiquitin , carcinogenesis , chemistry , biology , medicine , microbiology and biotechnology , biochemistry , gene
The epidermal growth factor receptor ( EGFR ) is implicated in many types of cancer, including colorectal cancer ( CRC ), and has become one of the most common candidates for targeted therapy. Here, we found that Erbin, a member of the leucine‐rich repeat and PDZ domain ( LAP ) family, plays a key role in EGFR signalling. Erbin inhibited EGFR ubiquitination and stabilized the EGFR protein by interacting with c‐Cbl. Moreover, the PDZ domain of Erbin was critical for the interaction between Erbin and c‐Cbl and EGFR ubiquitination. Interestingly, Erbin expression was elevated in tumour samples from CRC patients, increased in advanced clinical stage disease and correlated with EGFR expression. In vivo studies using mouse xenograft models of CRC showed that Erbin promotes tumour growth, and that the effects of Erbin on tumour growth are mainly related to the regulatory effects of Erbin on EGFR . The azoxymethane ( AOM )‐induced colon carcinogenesis model in Erbin ΔC / ΔC mice, with the PDZ domain of Erbin deleted, demonstrated that the PDZ domain of Erbin and its regulation of EGFR signalling are necessary for the tumourigenesis and tumour growth of CRC . We found that Erbin promotes tumourigenesis and tumour growth in CRC by stabilizing EGFR . Our study sheds light on developing Erbin, especially its PDZ domain, as a potential target for CRC treatment. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.