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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

The ability of Fe65 to suppress cell motility depends on HDAC6 status.WT and HDAC6 KO MEFs were transfected with control or Fe65 siRNA for 48 h. (A), Western blots were performed to show the efficient knockdown of Fe65 and β-actin blot was included to show even loading. (B), 4 × 104 cells were plated into trans-well inserts and cells were fixed and photographed 16 h after plating. (C), Quantitative data were presented as bar graphs and data statistics performed as described in Fig. 1.
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f3: The ability of Fe65 to suppress cell motility depends on HDAC6 status.WT and HDAC6 KO MEFs were transfected with control or Fe65 siRNA for 48 h. (A), Western blots were performed to show the efficient knockdown of Fe65 and β-actin blot was included to show even loading. (B), 4 × 104 cells were plated into trans-well inserts and cells were fixed and photographed 16 h after plating. (C), Quantitative data were presented as bar graphs and data statistics performed as described in Fig. 1.

Mentions: To further validate the role of HDAC6 in the Fe65 action, we investigated the effect of Fe65 knockdown on cell motility in wild type (WT) and HDAC6 (HDAC6 KO) mouse embryonic fibroblasts (MEFs). Although Fe65 siRNA decreased Fe65 protein expression to similar levels in WT and HDAC6 KO MEFs (Fig. 3A), it selectively increased migration and invasion of the WT, but not HDAC6 KO, MEFs (Fig. 3B). Quantitative data showed that the effect of Fe65 knockdown on the migration and invasion of WT MEFs is significant (Fig. 3C). Together with the HDAC inhibitor analyses in Fig. 2, the data from HDAC6 KO MEFs have clearly shown that the ability of Fe65 to suppress cell motility and invasion is sensitive to protein acetylation events controlled by HDAC6.


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)

The ability of Fe65 to suppress cell motility depends on HDAC6 status.WT and HDAC6 KO MEFs were transfected with control or Fe65 siRNA for 48 h. (A), Western blots were performed to show the efficient knockdown of Fe65 and β-actin blot was included to show even loading. (B), 4 × 104 cells were plated into trans-well inserts and cells were fixed and photographed 16 h after plating. (C), Quantitative data were presented as bar graphs and data statistics performed as described in Fig. 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: The ability of Fe65 to suppress cell motility depends on HDAC6 status.WT and HDAC6 KO MEFs were transfected with control or Fe65 siRNA for 48 h. (A), Western blots were performed to show the efficient knockdown of Fe65 and β-actin blot was included to show even loading. (B), 4 × 104 cells were plated into trans-well inserts and cells were fixed and photographed 16 h after plating. (C), Quantitative data were presented as bar graphs and data statistics performed as described in Fig. 1.
Mentions: To further validate the role of HDAC6 in the Fe65 action, we investigated the effect of Fe65 knockdown on cell motility in wild type (WT) and HDAC6 (HDAC6 KO) mouse embryonic fibroblasts (MEFs). Although Fe65 siRNA decreased Fe65 protein expression to similar levels in WT and HDAC6 KO MEFs (Fig. 3A), it selectively increased migration and invasion of the WT, but not HDAC6 KO, MEFs (Fig. 3B). Quantitative data showed that the effect of Fe65 knockdown on the migration and invasion of WT MEFs is significant (Fig. 3C). Together with the HDAC inhibitor analyses in Fig. 2, the data from HDAC6 KO MEFs have clearly shown that the ability of Fe65 to suppress cell motility and invasion is sensitive to protein acetylation events controlled by HDAC6.

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