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Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.

På svenska

Author

  • Christian Hansen
  • Paul Greengard
  • Angus C Nairn
  • Tommy Andersson
  • Wolfgang F Vogel

Summary, in English

Cell migration plays a central role in processes such as development, wound healing and cancer metastasis. Here we describe a novel interaction between DDR1, a receptor tyrosine kinase activated by collagen, and the phosphoprotein DARPP-32 in mammary epithelial cells. DARPP-32 expression was readily detected in non-transformed mammary cell lines, but was strongly reduced or even absent in breast tumor cell lines, such as MCF7. Transfection of MCF7 cells with DARPP-32 resulted in severely impaired cell migration, while DARPP-32 transfection into the DDR1-deficient breast cancer cell line MDA-MB-231 did not alter migration. Co-expression of both DDR1 and DARPP-32 in MDA-MB-231 cells inhibited migration, thereby supporting a critical role of the DDR1/DARPP-32 complex in motility. Mutational substitution of the phosphorylation sites Thr-34 or Thr-75 on DARPP-32 revealed that phosphorylation of Thr-34 is necessary for the ability of DARPP-32 to impair breast tumor cell migration. Thus, DARPP-32 signaling downstream of DDR1 is a potential new target for effective anti-metastatic breast cancer therapy.

Department/s

Publishing year

2006

Language

English

Pages

4011-4018

Publication/Series

Experimental Cell Research

Volume

312

Issue

20

Document type

Journal article

Publisher

Academic Press

Topic

  • Cancer and Oncology

Keywords

  • cell invasion
  • cancer
  • breast
  • discoidin domain
  • phosphorylation
  • cell migration
  • collagen
  • tyrosine kinase

Status

Published

Research group

  • Molecular Neurobiology
  • Experimental Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1090-2422