Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/162409
- author
- Hansen, Christian LU ; Greengard, Paul ; Nairn, Angus C ; Andersson, Tommy LU and Vogel, Wolfgang F
- organization
- publishing date
- 2006
- 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
- pmid:17027969
- 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
- 2016-04-01 12:03:46
- date last changed
- 2022-03-05 18:22:17
@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}}, keywords = {{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}}, doi = {{10.1016/j.yexcr.2006.09.003}}, volume = {{312}}, year = {{2006}}, }