Abstract
ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E4429-E4438 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 111 |
| Issue number | 42 |
| DOIs | |
| State | Published - Oct 21 2014 |
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Keywords
- Breast cancer
- ErbB2
- Erbin
- HSP90
- Stability
ASJC Scopus subject areas
- General
Cite this
Role of Erbin in ErbB2-dependent breast tumor growth. / Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wencheng; Borg, Jean Paul; Mei, Lin.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 42, 21.10.2014, p. E4429-E4438.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of Erbin in ErbB2-dependent breast tumor growth
AU - Tao, Yanmei
AU - Shen, Chengyong
AU - Luo, Shiwen
AU - Traoré, Wilfried
AU - Marchetto, Sylvie
AU - Santoni, Marie Josée
AU - Xu, Linlin
AU - Wu, Biao
AU - Shi, Chao
AU - Mei, Jinghong
AU - Bates, Ryan
AU - Liu, Xihui
AU - Zhao, Kai
AU - Xiong, Wencheng
AU - Borg, Jean Paul
AU - Mei, Lin
PY - 2014/10/21
Y1 - 2014/10/21
N2 - ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.
AB - ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.
KW - Breast cancer
KW - ErbB2
KW - Erbin
KW - HSP90
KW - Stability
UR - http://www.scopus.com/inward/record.url?scp=84908065149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908065149&partnerID=8YFLogxK
U2 - 10.1073/pnas.1407139111
DO - 10.1073/pnas.1407139111
M3 - Article
C2 - 25288731
AN - SCOPUS:84908065149
VL - 111
SP - E4429-E4438
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 42
ER -