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

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

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.

Greengard, Paul (författare)
Nairn, Angus C (författare)
Andersson, TommyLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups(Swepub:lu)expp-tan (författare)
Vogel, Wolfgang F (författare)
Molekylär neurobiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Ingår i:Experimental Cell Research: Elsevier BV312:20, s. 4011-40181090-24220014-4827

Av författaren/redakt...: Hansen, Christia ...; Greengard, Paul; Nairn, Angus C; Andersson, Tommy; Vogel, Wolfgang ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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