N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation

James Hulit, Kimita Suyama, Su Chung, Rinat Keren, Georgia Agiostratidou, Weisong Shan, Xinyuan Dong, Terence M. Williams, Michael P. Lisanti, Karen Knudsen, Rachel Hazan

Research output: Contribution to journalArticle

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Abstract

N-cadherin is up-regulated in aggressive breast carcinomas, but its mechanism of action in vivo remains unknown. Transgenic mice coexpressing N-cadherin and polyomavirus middle T antigen (PyVmT) in the mammary epithelium displayed increased pulmonary metastasis, with no differences in tumor onset or growth relative to control PyVmT mice. PyVmT-N-cadherin tumors contained higher levels of phosphorylated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) than PyVmT controls, and phosphorylated ERK staining was further increased in pulmonary metastases. Tumor cell isolates from PyVmT-N-cadherin mice exhibited enhanced ERK activation, motility, invasion, and matrix metalloproteinase-9 (MMP-9) expression relative to PyVmT controls. MAPK/ERK kinase 1 inhibition in PyVmT-N-cadherin cells reduced MMP-9 production and invasion but not motility. Furthermore, inactivation of fibroblast growth factor receptor in PyVmT-N-cadherin cells reduced motility, invasion, and ERK activation but had no effect on PyVmT cells. Thus, de novo expression of N-cadherin in mammary ducts enhances metastasis of breast tumors via enhanced ERK signaling.

Original languageEnglish (US)
Pages (from-to)3106-3116
Number of pages11
JournalCancer Research
Volume67
Issue number7
DOIs
StatePublished - Apr 1 2007

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Polyomavirus Transforming Antigens
Extracellular Signal-Regulated MAP Kinases
Cadherins
Breast Neoplasms
Neoplasm Metastasis
Matrix Metalloproteinase 9
Breast
Fibroblast Growth Factor Receptors
Neoplasms
Lung
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Transgenic Mice
Cell Movement
Phosphotransferases
Epithelium
Staining and Labeling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation. / Hulit, James; Suyama, Kimita; Chung, Su; Keren, Rinat; Agiostratidou, Georgia; Shan, Weisong; Dong, Xinyuan; Williams, Terence M.; Lisanti, Michael P.; Knudsen, Karen; Hazan, Rachel.

In: Cancer Research, Vol. 67, No. 7, 01.04.2007, p. 3106-3116.

Research output: Contribution to journalArticle

Hulit, J, Suyama, K, Chung, S, Keren, R, Agiostratidou, G, Shan, W, Dong, X, Williams, TM, Lisanti, MP, Knudsen, K & Hazan, R 2007, 'N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation', Cancer Research, vol. 67, no. 7, pp. 3106-3116. https://doi.org/10.1158/0008-5472.CAN-06-3401
Hulit, James ; Suyama, Kimita ; Chung, Su ; Keren, Rinat ; Agiostratidou, Georgia ; Shan, Weisong ; Dong, Xinyuan ; Williams, Terence M. ; Lisanti, Michael P. ; Knudsen, Karen ; Hazan, Rachel. / N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation. In: Cancer Research. 2007 ; Vol. 67, No. 7. pp. 3106-3116.
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