Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.
Författare
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.
Avdelning/ar
- Molecular Neurobiology
- Experimentell patologi, Malmö
Publiceringsår
2006
Språk
Engelska
Sidor
4011-4018
Publikation/Tidskrift/Serie
Experimental Cell Research
Volym
312
Issue
20
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Academic Press
Ämne
- Cancer and Oncology
Nyckelord
- cell invasion
- cancer
- breast
- discoidin domain
- phosphorylation
- cell migration
- collagen
- tyrosine kinase
Status
Published
Forskningsgrupp
- Molecular Neurobiology
- Experimental Pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1090-2422