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

Hansen, Christian (author): Lund University,Lunds universitet,Molekylär neurobiologi,Forskargrupper vid Lunds universitet,Experimentell patologi, Malmö,Molecular Neurobiology,Lund University Research Groups,Experimental Pathology, Malmö

Greengard, Paul (author)

Nairn, Angus C (author)

Andersson, Tommy (author): Lund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups

Vogel, Wolfgang F (author)

(creator_code:org_t)

Elsevier BV, 2006
2006
English.
In: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 312:20, s. 4011-4018

Related links:: http://www.ncbi.nlm....; show more...; http://dx.doi.org/10...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Hansen, Christia ...; Greengard, Paul; Nairn, Angus C; Andersson, Tommy; Vogel, Wolfgang ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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