Abelson interactor protein-1 positively regulates breast cancer cell proliferation, migration, and invasion.
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.
Wang
Chunjie
C
Division of Applied Molecular Oncology, Ontario Cancer Institute, Toronto, Ontario, Canada.
Navab
Roya
R
Iakovlev
Vladimir
V
Leng
Yan
Y
Zhang
Jinyi
J
Tsao
Ming-Sound
MS
Siminovitch
Katherine
K
McCready
David R
DR
Done
Susan J
SJ
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia; D034741:RNA, Small Interfering / Q000494:pharmacology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D012359:tRNA Methyltransferases
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D051300:Wiskott-Aldrich Syndrome Protein Family; D012359:tRNA Methyltransferases; C513733:ABI1 protein, human; C518673:CYFIP2 protein, human; C120152:WASF2 protein, human; C498548:TRMO protein, human