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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 inhibits invadopodia formation in breast cancer cells.(A), MDA-MB-231 cells stably expressing control or Fe65 shRNA were plated onto gelatin-coated glass coverslips and stained for cortactin (green), F-actin (phalloidin, red) and DAPI (blue). Representative immunofluorescence images were included to show invadopodia underneath the cells as orange dots in the merged panels. Quantitative data were presented as bar graphs to show the difference between control and Fe65 knockdown cells. Each data point represents the counting of 30 cells. Values are means ± SD. Statistical analyses were performed with student’s t test (1 tailed distribution). (B), A model depicting our current understanding how Fe65 suppresses breast cancer migration and invasion through the recruitment of Tip60 that opposes the activity of HDAC6 on cortactin acetylation.
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f6: Fe65 inhibits invadopodia formation in breast cancer cells.(A), MDA-MB-231 cells stably expressing control or Fe65 shRNA were plated onto gelatin-coated glass coverslips and stained for cortactin (green), F-actin (phalloidin, red) and DAPI (blue). Representative immunofluorescence images were included to show invadopodia underneath the cells as orange dots in the merged panels. Quantitative data were presented as bar graphs to show the difference between control and Fe65 knockdown cells. Each data point represents the counting of 30 cells. Values are means ± SD. Statistical analyses were performed with student’s t test (1 tailed distribution). (B), A model depicting our current understanding how Fe65 suppresses breast cancer migration and invasion through the recruitment of Tip60 that opposes the activity of HDAC6 on cortactin acetylation.

Mentions: Invadopodia are F-actin driven adhesive membrane protrusions that coordinate extracellular matrix degradation and invasion in cancer cells4546. The binding of Fe65 to cortactin suggests that Fe65 may regulate invadopodia formation. As shown in Fig. 6A, stable Fe65 knockdown significantly increased invadopodia formation in MDA-MB-231 cells as measured by co-immunofluorescence staining of cortactin and F-actin (with phalloidin). The data suggest a negative role of Fe65 in invadopodia formation, possibly through the increased cortactin acetylation, which is known to decrease its interaction with F-actin15.


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 inhibits invadopodia formation in breast cancer cells.(A), MDA-MB-231 cells stably expressing control or Fe65 shRNA were plated onto gelatin-coated glass coverslips and stained for cortactin (green), F-actin (phalloidin, red) and DAPI (blue). Representative immunofluorescence images were included to show invadopodia underneath the cells as orange dots in the merged panels. Quantitative data were presented as bar graphs to show the difference between control and Fe65 knockdown cells. Each data point represents the counting of 30 cells. Values are means ± SD. Statistical analyses were performed with student’s t test (1 tailed distribution). (B), A model depicting our current understanding how Fe65 suppresses breast cancer migration and invasion through the recruitment of Tip60 that opposes the activity of HDAC6 on cortactin acetylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Fe65 inhibits invadopodia formation in breast cancer cells.(A), MDA-MB-231 cells stably expressing control or Fe65 shRNA were plated onto gelatin-coated glass coverslips and stained for cortactin (green), F-actin (phalloidin, red) and DAPI (blue). Representative immunofluorescence images were included to show invadopodia underneath the cells as orange dots in the merged panels. Quantitative data were presented as bar graphs to show the difference between control and Fe65 knockdown cells. Each data point represents the counting of 30 cells. Values are means ± SD. Statistical analyses were performed with student’s t test (1 tailed distribution). (B), A model depicting our current understanding how Fe65 suppresses breast cancer migration and invasion through the recruitment of Tip60 that opposes the activity of HDAC6 on cortactin acetylation.
Mentions: Invadopodia are F-actin driven adhesive membrane protrusions that coordinate extracellular matrix degradation and invasion in cancer cells4546. The binding of Fe65 to cortactin suggests that Fe65 may regulate invadopodia formation. As shown in Fig. 6A, stable Fe65 knockdown significantly increased invadopodia formation in MDA-MB-231 cells as measured by co-immunofluorescence staining of cortactin and F-actin (with phalloidin). The data suggest a negative role of Fe65 in invadopodia formation, possibly through the increased cortactin acetylation, which is known to decrease its interaction with F-actin15.

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