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. (Mol Cancer Res 2007;5(10):1031–9)

[1]  J. Brugge,et al.  Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition , 2005, The Journal of cell biology.

[2]  Z. Duan,et al.  Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines , 2005, Cancer Chemotherapy and Pharmacology.

[3]  Hoffman Fm,et al.  Drosophila abelson interacting protein (dAbi) is a positive regulator of abelson tyrosine kinase activity. , 1999 .

[4]  K. Siminovitch,et al.  Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Goff,et al.  Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. , 1995, Genes & development.

[6]  C. Piccoli,et al.  Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth , 1997, Oncogene.

[7]  A. Toker,et al.  Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. , 2005, Molecular cell.

[8]  Pnina Brodt,et al.  Inhibition of carcinoma cell invasion and liver metastases formation by the cysteine proteinase inhibitor E-64 , 1997, Clinical & Experimental Metastasis.

[9]  K. Rottner,et al.  Sra‐1 and Nap1 link Rac to actin assembly driving lamellipodia formation , 2004, The EMBO journal.

[10]  Karsten Schlüns,et al.  Patterns of chromosomal imbalances in invasive breast cancer , 2000, International journal of cancer.

[11]  T. Taki,et al.  t(10;11)‐Acute leukemias with MLL‐AF10 and MLL‐ABI1 chimeric transcripts: Specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines , 2001, Genes, chromosomes & cancer.

[12]  S. Goff,et al.  Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1 , 2001, Oncogene.

[13]  J. Juang,et al.  Drosophila Abelson interacting protein (dAbi) is a positive regulator of Abelson tyrosine kinase activity , 1999, Oncogene.

[14]  A. Pendergast,et al.  Abl Interactor 1 (Abi-1) Wave-Binding and SNARE Domains Regulate Its Nucleocytoplasmic Shuttling, Lamellipodium Localization, and Wave-1 Levels , 2004, Molecular and Cellular Biology.

[15]  P. Zipfel,et al.  Role for the Abi/Wave Protein Complex in T Cell Receptor-Mediated Proliferation and Cytoskeletal Remodeling , 2006, Current Biology.

[16]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[17]  K. Rottner,et al.  The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia , 2001, Current Biology.

[18]  B. Isaac,et al.  A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages , 2005, Journal of Cell Science.

[19]  J. Jakus,et al.  E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor. , 2005, Experimental cell research.

[20]  T. Stradal,et al.  Protein complexes regulating Arp2/3-mediated actin assembly. , 2006, Current opinion in cell biology.

[21]  G. Scita,et al.  Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1 , 2003, The Journal of cell biology.

[22]  J. Dennis,et al.  Tumor Cell Pseudopodial Protrusions , 2005, Journal of Biological Chemistry.

[23]  A. Ridley.  Rho GTPases and cell migration. , 2001, Journal of cell science.

[24]  M. Lacroix,et al.  Relevance of Breast Cancer Cell Lines as Models for Breast Tumours: An Update , 2004, Breast Cancer Research and Treatment.

[25]  K. Rottner,et al.  Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes , 2005, Nature Cell Biology.

[26]  C. Micalizzi,et al.  Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia? , 2002, Cancer genetics and cytogenetics.

[27]  S. Goff,et al.  Abl Interactor 1 Binds to Sos and Inhibits Epidermal Growth Factor- and v-Abl-Induced Activation of Extracellular Signal-Regulated Kinases , 2000, Molecular and Cellular Biology.

[28]  D. Cortez,et al.  Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. , 1998, Genes & development.

[29]  Y. Hayashi,et al.  ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23). , 1998, Blood.

[30]  Yusuke Nakamura,et al.  Genome-wide analysis of organ-preferential metastasis of human small cell lung cancer in mice. , 2003, Molecular cancer research : MCR.

[31]  Andrea Disanza,et al.  Abi1 is essential for the formation and activation of a WAVE2 signalling complex , 2004, Nature Cell Biology.

[32]  M. Rubin,et al.  Loss of expression of human spectrin src homology domain binding protein 1 is associated with 10p loss in human prostatic adenocarcinoma. , 2001, Neoplasia.