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Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.

Sun Y, Sun J, Lungchukiet P, Quarni W, Yang S, Zhang X, Bai W - Sci Rep (2015)

Bottom Line: The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion.Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation.The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL 33612.

ABSTRACT
Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer's disease, but little is known about its functions in cancer cells. The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion. Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation. The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.

No MeSH data available.


Related in: MedlinePlus

Fe65 binds to cortactin to inhibit cell motility through its PTB1 domain.(A), 293T cells were transfected with 1.5 μg Flag-cortactin and/or 1.5 μg of Myc-Fe65. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (B), 293T cells were transfected with 1.5 μg Flag-cortactin and 1.5 μg of Myc-Fe65 or deletion constructs as indicated. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (C), 293T cells were transfected with Myc-Fe65 or deletion constructs as indicated. 5 × 105 transfected cells were plated into trans-well inserts 24 h post transfections. Cells were fixed and photographed 36 h after plating. (D) and (E), Quantitative data were presented as bar graphs and data statistics were performed as described in Fig. 1. a, p < 0.01; b, p > 0.05.
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f4: Fe65 binds to cortactin to inhibit cell motility through its PTB1 domain.(A), 293T cells were transfected with 1.5 μg Flag-cortactin and/or 1.5 μg of Myc-Fe65. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (B), 293T cells were transfected with 1.5 μg Flag-cortactin and 1.5 μg of Myc-Fe65 or deletion constructs as indicated. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (C), 293T cells were transfected with Myc-Fe65 or deletion constructs as indicated. 5 × 105 transfected cells were plated into trans-well inserts 24 h post transfections. Cells were fixed and photographed 36 h after plating. (D) and (E), Quantitative data were presented as bar graphs and data statistics were performed as described in Fig. 1. a, p < 0.01; b, p > 0.05.

Mentions: Because HDAC6 deacetylates cortactin to promote cell motility15, its involvement in the regulation of breast cancer cell invasion by Fe65 prompted us to investigate the possible interaction between Fe65 and cortactin. 293T cells were co-transfected with Flag-tagged cortactin and Myc-tagged Fe65 and co-immunoprecipitations performed. As shown in Fig. 4A, Flag beads co-precipitated Fe65 and cortactin in co-transfected cells. The co-precipitations reflect a true interaction between Fe65 and cortactin because the Flag beads did not precipitate Fe65 in cells transfected with Fe65 without Flag-cortactin.


Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.

Sun Y, Sun J, Lungchukiet P, Quarni W, Yang S, Zhang X, Bai W - Sci Rep (2015)

Fe65 binds to cortactin to inhibit cell motility through its PTB1 domain.(A), 293T cells were transfected with 1.5 μg Flag-cortactin and/or 1.5 μg of Myc-Fe65. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (B), 293T cells were transfected with 1.5 μg Flag-cortactin and 1.5 μg of Myc-Fe65 or deletion constructs as indicated. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (C), 293T cells were transfected with Myc-Fe65 or deletion constructs as indicated. 5 × 105 transfected cells were plated into trans-well inserts 24 h post transfections. Cells were fixed and photographed 36 h after plating. (D) and (E), Quantitative data were presented as bar graphs and data statistics were performed as described in Fig. 1. a, p < 0.01; b, p > 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4499803&req=5

f4: Fe65 binds to cortactin to inhibit cell motility through its PTB1 domain.(A), 293T cells were transfected with 1.5 μg Flag-cortactin and/or 1.5 μg of Myc-Fe65. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (B), 293T cells were transfected with 1.5 μg Flag-cortactin and 1.5 μg of Myc-Fe65 or deletion constructs as indicated. Cellular extracts were subjected to co-immunoprecipitation analyses with antibodies as indicated. (C), 293T cells were transfected with Myc-Fe65 or deletion constructs as indicated. 5 × 105 transfected cells were plated into trans-well inserts 24 h post transfections. Cells were fixed and photographed 36 h after plating. (D) and (E), Quantitative data were presented as bar graphs and data statistics were performed as described in Fig. 1. a, p < 0.01; b, p > 0.05.
Mentions: Because HDAC6 deacetylates cortactin to promote cell motility15, its involvement in the regulation of breast cancer cell invasion by Fe65 prompted us to investigate the possible interaction between Fe65 and cortactin. 293T cells were co-transfected with Flag-tagged cortactin and Myc-tagged Fe65 and co-immunoprecipitations performed. As shown in Fig. 4A, Flag beads co-precipitated Fe65 and cortactin in co-transfected cells. The co-precipitations reflect a true interaction between Fe65 and cortactin because the Flag beads did not precipitate Fe65 in cells transfected with Fe65 without Flag-cortactin.

Bottom Line: The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion.Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation.The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL 33612.

ABSTRACT
Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer's disease, but little is known about its functions in cancer cells. The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion. Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation. The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.

No MeSH data available.


Related in: MedlinePlus