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Watertown, MA, United States

Suzuki M.,Sapporo Medical University | Iwasaki M.,Sapporo Medical University | Sugio A.,Sapporo Medical University | Hishiya A.,The Boston Biomedical Research Institute | And 5 more authors.
Cancer Letters | Year: 2011

BAG3 (BCL2-associated athanogene 3) is a member of the BAG family proteins, which interact with and regulate Hsp70. Our aim in the present study was to correlate BAG3 expression in ovarian cancer with invasion and progression-free survival. We found that BAG3 interacts with MMP2 in cultured ovarian cancer cells, and that knockdown of BAG3 expression downregulated MMP2 expression and diminished cell motility and invasiveness. The incidence of BAG3 positivity was significantly higher at advanced clinical stages of ovarian cancer than at early stages. We suggest that BAG3 binds to MMP2 to positively regulate the process of cell invasion. © 2011 Elsevier Ireland Ltd. Source


Iwasaki M.,Georgia Regents University | Tanaka R.,The Boston Biomedical Research Institute | Hishiya A.,The Boston Biomedical Research Institute | Homma S.,Sanford Burnham Institute for Medical Research | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

BAG3, a member of the Hsc70 binding co-chaperone BAG-family proteins, has critical roles in regulating actin organization, cell adhesion, cell motility and tumor metastasis. The PDZ domain containing guanine nucleotide exchange factor 2 (PDZGEF2) was cloned as a BAG3-interacting protein. PDZGEF2 induces activation of Rap1 and increases integrin-mediated cell adhesion. The PPDY motif at the C-terminus of PDZGEF2 binds to the WW domain of BAG3 in vitro and in vivo. BAG3 deletion mutant lacking the WW domain lose its cell adhesion and motility activity. Gene knockdown of PDZGEF2 leads to the loss of cell adhesion on fibronectin-coated plates while BAG3 overexpression increases cell adhesion in Cos7 cells, but not in PDZGEF2 gene knockdown cells indicating that PDZGEF2 is a critical partner for BAG3 in regulating cell adhesion. © 2010 Elsevier Inc. Source

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