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Angiogenesis, Metastasis, and the Cellular Microenvironment

Abelson Interactor Protein-1 Positively Regulates Breast Cancer Cell Proliferation, Migration, and Invasion

¹ Division of Applied Molecular Oncology, Ontario Cancer Institute; Departments of ² Laboratory Medicine and Pathobiology and ³ Medical Biophysics, University of Toronto; ⁴ The Samuel Lunenfeld Research Institute, Mount Sinai Hospital; and ⁵ Department of Surgical Oncology, University Health Network, Toronto, Ontario, Canada

Requests for reprints: Susan J. Done, Division of Applied Molecular Oncology, Ontario Cancer Institute, 610 University Avenue, Room 10-717, Toronto, Ontario, Canada M5G 2M9. Phone: 416-946-2337; Fax: 416-340-5517. E-mail: sdone{at}uhnres.utoronto.ca

Abelson interactor protein-1 (ABI-1) is an adaptor protein involved in actin reorganization and lamellipodia formation. It forms a macromolecular complex containing Hspc300/WASP family verprolin-homologous proteins 2/ABI-1/nucleosome assembly protein 1/PIR121 or Abl/ABI-1/WASP family verprolin-homologous proteins 2 in response to Rho family-dependent stimuli. Due to its role in cell mobility, we hypothesized that ABI-1 has a role in invasion and metastasis. In the present study, we found that weakly invasive breast cancer cell lines (MCF-7, T47D, MDA-MB-468, SKBR3, and CAMA1) express lower levels of ABI-1 compared with highly invasive breast cancer cell lines (MDA-MB-231, MDA-MB-157, BT549, and Hs578T), which exhibit high ABI-1 levels. Using RNA interference, ABI-1 was stably down-regulated in MDA-MB-231, which resulted in decreased cell proliferation and anchorage-dependent colony formation and abrogation of lamellipodia formation on fibronectin. Down-regulation of ABI-1 decreased invasiveness and migration ability and decreased adhesion on collagen IV and actin polymerization in MDA-MB-231 cells. Additionally, compared with control parental cells, ABI-1 small interfering RNA–transfected cells showed decreased levels of phospho-PDK1, phospho-Raf, phospho-AKT, total AKT, and AKT1. These data suggest that ABI-1 plays an important role in the spread of breast cancer and that this role may be mediated via the phosphatidylinositol 3-kinase pathway. (Mol Cancer Res 2007;5(10):1031–9)