Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies

Shahin Assefnia, Sivanesan Dakshanamurthy, Jaime M.Guidry Auvil, Constanze Hampel, Panos Z. Anastasiadis, Bhaskar Kallakury, Aykut Uren, David W. Foley, Milton L. Brown, Lawrence Shapiro, Michael Brenner, David Haigh, Stephen W. Byers

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in development, poor prognosis malignancies and cancer stem cells, is also a major therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis. We show that CDH11 is increased early in breast cancer and ductal carcinoma in-situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basallike breast tumors and decreased proliferation and colony formation of breast, glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib, which binds to CDH11, and other small molecules designed to bind CDH11 without inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells in vitro and in animals. These data suggest that CDH11 is important for malignant progression, and is a therapeutic target in arthritis and cancer with the potential for rapid clinical translation.

Original languageEnglish (US)
Pages (from-to)1458-1474
Number of pages17
JournalOncotarget
Volume5
Issue number6
DOIs
StatePublished - 2014

Keywords

  • Breast cancer
  • Cadherin-11
  • Celecoxib
  • Glioblastoma
  • Rheumatoid arthritis
  • Small molecule inhibitor

ASJC Scopus subject areas

  • Oncology

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    Assefnia, S., Dakshanamurthy, S., Auvil, J. M. G., Hampel, C., Anastasiadis, P. Z., Kallakury, B., Uren, A., Foley, D. W., Brown, M. L., Shapiro, L., Brenner, M., Haigh, D., & Byers, S. W. (2014). Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies. Oncotarget, 5(6), 1458-1474. https://doi.org/10.18632/oncotarget.1538