Role of Erbin in ErbB2-dependent breast tumor growth

Yanmei Tao, Chengyong Shen, Shiwen Luo, Wilfried Traoré, Sylvie Marchetto, Marie Josée Santoni, Linlin Xu, Biao Wu, Chao Shi, Jinghong Mei, Ryan Bates, Xihui Liu, Kai Zhao, Wen Cheng Xiong, Jean Paul Borg, Lin Mei

Research output: Contribution to journalArticle

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)E4429-E4438
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number42
DOIs
StatePublished - Oct 21 2014

Keywords

  • Breast cancer
  • ErbB2
  • Erbin
  • HSP90
  • Stability

ASJC Scopus subject areas

  • General

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  • Cite this

    Tao, Y., Shen, C., Luo, S., Traoré, W., Marchetto, S., Santoni, M. J., Xu, L., Wu, B., Shi, C., Mei, J., Bates, R., Liu, X., Zhao, K., Xiong, W. C., Borg, J. P., & Mei, L. (2014). Role of Erbin in ErbB2-dependent breast tumor growth. Proceedings of the National Academy of Sciences of the United States of America, 111(42), E4429-E4438. https://doi.org/10.1073/pnas.1407139111