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

Hansen, Christian LU ; Greengard, Paul; Nairn, Angus C; Andersson, Tommy LU and Vogel, Wolfgang F (2006) In Experimental Cell Research 312(20). p.4011-4018
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell invasion, cancer, breast, discoidin domain, phosphorylation, cell migration, collagen, tyrosine kinase
in
Experimental Cell Research
volume
312
issue
20
pages
4011 - 4018
publisher
Academic Press
external identifiers
  • wos:000242838100005
  • scopus:34447651165
ISSN
1090-2422
DOI
10.1016/j.yexcr.2006.09.003
language
English
LU publication?
yes
id
0942c2a4-3038-490b-a4bd-f5e9c42bbf32 (old id 162409)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17027969&dopt=Abstract
date added to LUP
2007-07-25 10:43:26
date last changed
2019-05-28 01:38:23
@article{0942c2a4-3038-490b-a4bd-f5e9c42bbf32,
  abstract     = {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.},
  author       = {Hansen, Christian and Greengard, Paul and Nairn, Angus C and Andersson, Tommy and Vogel, Wolfgang F},
  issn         = {1090-2422},
  keyword      = {cell invasion,cancer,breast,discoidin domain,phosphorylation,cell migration,collagen,tyrosine kinase},
  language     = {eng},
  number       = {20},
  pages        = {4011--4018},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2006.09.003},
  volume       = {312},
  year         = {2006},
}