The Function Of Abl Interactor Proteins In P185 Bcr-Abl Transformed Leukemic And Breast Cancer Cells

Ab1 interactor(Abi) is a key regulator of actin polymerization/depolymerization.The involvement of Abi in the development of abnormal cytoskeletal functions of cancer cells has recently been reported.Bcr-Ab1 downregulating Abi2 expression in hematopoietic cells is already known.In this study,we mapped the protein sequence required for Abi2 degradation.We found the different isoforms of Abi may play different role in cell processes. Abi1 and Abi2B/A could increase the MMP9 and ID1 expression in breast cancer cells,whereas Abi2A couldn't.Also we report here a novel function for Abi1 in the regulation of invadopodia formation and Src-Id1-matrix metalloproteinase 9(MMP-9) pathway in MDA-MB231 human breast cancer cells.Abi1 is found in the invadopodia of MDA-MB231 cells.Epigenetic silencing of the Abi1 gene by short hairpin RNA(shRNA) in MDA-MB231 cells impaired the formation of invadopodia and resulted in down-regulation of the Scr activation and Id1/MMP-9 expression.The decreased invadopodia formation and MMP-9 expression correlate with a reduction in the ability of these cells to degrade extracellular matrix (ECM).Remarkably,the knockdown of Abi1 expression inhibited tumor cell proliferation and migration in vitro,and slowed tumor growth in vivo.Taken together,these results indicate that the Abi1 signaling plays a critical role in breast cancer progression and suggest that this pathway may serve as a therapeutic target for the treatment of human breast cancer.