Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Luis Castro-Sanchez Adriana Soto-Guzman Margarita Guaderrama-Diaz Pedro Cortes-Reynosa Eduardo Perez Salazar
- چاپ و سال / کشور: 2011
Description
Discoidin domain receptors (DDRs) are receptor tyrosine kinases that get activated by collagens in its native triple-helical form. In mammalian cells, DDR family consists of two members, namely DDR1 and DDR2, which mediates migration and proliferation of several cell types. DDR1 is activated by native type IV collagen and overexpressed in human breast cancer. Type IV collagen is the main component of basement membrane (BM), and the ability to degrade and penetrate BM is related with an increased potential for invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that collectively are capable of degrading all components of the extracellular matrix, including the BM. In breast cancer cells, denatured type IV collagen induces MMP-9 secretion and invasion. However, the role of DDR1 in the regulation of gelatinases (MMP-2 and -9) secretion and invasion in breast cancer cells remains to be studied. We demonstrate here that native type IV collagen induces MMP-2 and -9 secretions and invasion through a DDR1 and Src-dependent pathway, together with an increase of MMP-2 and -9-cell surface levels. MMP-2 and -9 secretions require PKC kinase activity, epidermal growth factor receptor (EGFR) activation, arachidonic acid (AA) production and AA metabolites in MDA-MB-231 breast cancer cells. In summary, our data demonstrate, for the first time, that DDR1 mediates MMP-2 and -9 secretions and invasion induced by native type IV collagen in MDA-MB-231 breast cancer cells.
Clin Exp Metastasis (2011) 28:463–477 DOI 10.1007/s10585-011-9385-9 Received: 8 October 2010 / Accepted: 21 March 2011 / Published online: 2 April 2011
