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

Shahin Assefnia, Sivanesan Dakshanamurthy, Jaime M Guidry Auvil, Constanze Hampel, Panagiotis 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

24 Citations (Scopus)

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
StatePublished - 2014

Fingerprint

Rheumatoid Arthritis
Neoplasms
Breast Neoplasms
Therapeutics
Celecoxib
Arthritis
Drug Repositioning
osteoblast cadherin
Carcinoma, Intraductal, Noninfiltrating
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Glioblastoma
Growth
Prostatic Neoplasms
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Assefnia, S., Dakshanamurthy, S., Auvil, J. M. G., Hampel, C., Anastasiadis, P. Z., Kallakury, B., ... Byers, S. W. (2014). Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies. Oncotarget, 5(6), 1458-1474.

Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis : Common target, common therapies. / Assefnia, Shahin; Dakshanamurthy, Sivanesan; Auvil, Jaime M Guidry; Hampel, Constanze; Anastasiadis, Panagiotis Z; Kallakury, Bhaskar; Uren, Aykut; Foley, David W.; Brown, Milton L.; Shapiro, Lawrence; Brenner, Michael; Haigh, David; Byers, Stephen W.

In: Oncotarget, Vol. 5, No. 6, 2014, p. 1458-1474.

Research output: Contribution to journalArticle

Assefnia, S, Dakshanamurthy, S, Auvil, JMG, Hampel, C, Anastasiadis, PZ, Kallakury, B, Uren, A, Foley, DW, Brown, ML, Shapiro, L, Brenner, M, Haigh, D & Byers, SW 2014, 'Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies', Oncotarget, vol. 5, no. 6, pp. 1458-1474.
Assefnia S, Dakshanamurthy S, Auvil JMG, Hampel C, Anastasiadis PZ, Kallakury B et al. Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies. Oncotarget. 2014;5(6):1458-1474.
Assefnia, Shahin ; Dakshanamurthy, Sivanesan ; Auvil, Jaime M Guidry ; Hampel, Constanze ; Anastasiadis, Panagiotis Z ; Kallakury, Bhaskar ; Uren, Aykut ; Foley, David W. ; Brown, Milton L. ; Shapiro, Lawrence ; Brenner, Michael ; Haigh, David ; Byers, Stephen W. / Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis : Common target, common therapies. In: Oncotarget. 2014 ; Vol. 5, No. 6. pp. 1458-1474.
@article{1b950a2ccfd742389a7cb5d6c0a7b94f,
title = "Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: Common target, common therapies",
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.",
keywords = "Breast cancer, Cadherin-11, Celecoxib, Glioblastoma, Rheumatoid arthritis, Small molecule inhibitor",
author = "Shahin Assefnia and Sivanesan Dakshanamurthy and Auvil, {Jaime M Guidry} and Constanze Hampel and Anastasiadis, {Panagiotis Z} and Bhaskar Kallakury and Aykut Uren and Foley, {David W.} and Brown, {Milton L.} and Lawrence Shapiro and Michael Brenner and David Haigh and Byers, {Stephen W.}",
year = "2014",
language = "English (US)",
volume = "5",
pages = "1458--1474",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "6",

}

TY - JOUR

T1 - Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis

T2 - Common target, common therapies

AU - Assefnia, Shahin

AU - Dakshanamurthy, Sivanesan

AU - Auvil, Jaime M Guidry

AU - Hampel, Constanze

AU - Anastasiadis, Panagiotis Z

AU - Kallakury, Bhaskar

AU - Uren, Aykut

AU - Foley, David W.

AU - Brown, Milton L.

AU - Shapiro, Lawrence

AU - Brenner, Michael

AU - Haigh, David

AU - Byers, Stephen W.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Cadherin-11

KW - Celecoxib

KW - Glioblastoma

KW - Rheumatoid arthritis

KW - Small molecule inhibitor

UR - http://www.scopus.com/inward/record.url?scp=84904251524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904251524&partnerID=8YFLogxK

M3 - Article

C2 - 24681547

AN - SCOPUS:84904251524

VL - 5

SP - 1458

EP - 1474

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 6

ER -