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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 cell motility in breast cancer cells.(A), 5 × 104 control or Fe65 stable knockdown MDA-MB-231 cells were plated into trans-well inserts and 3% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 8 h after plating. (B), 5 × 104 control or Fe65 stable knockdown MDA-MB-361 cells were plated into trans-well inserts and 5% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 16 h after plating. Western blots show efficient Fe65 knockdown and β-actin blots are included as loading controls. Quantitative data are shown as bar graphs with each data point representing analyses in duplicate performed in parallel that were repeated three times (n = 6). Values are means ± SD. P-values were calculated with student’s t test (1 tailed distribution).
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f1: Fe65 inhibits cell motility in breast cancer cells.(A), 5 × 104 control or Fe65 stable knockdown MDA-MB-231 cells were plated into trans-well inserts and 3% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 8 h after plating. (B), 5 × 104 control or Fe65 stable knockdown MDA-MB-361 cells were plated into trans-well inserts and 5% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 16 h after plating. Western blots show efficient Fe65 knockdown and β-actin blots are included as loading controls. Quantitative data are shown as bar graphs with each data point representing analyses in duplicate performed in parallel that were repeated three times (n = 6). Values are means ± SD. P-values were calculated with student’s t test (1 tailed distribution).

Mentions: In previous studies, it was noted that Fe65 was expressed at high levels in the cytoplasm of invasive breast cancer cells such as MDA-MB-231 and MDA-MB-36142, suggesting a possible role of Fe65 in controlling breast cancer invasion. To test this, Fe65 stable knockdown clones were established and the effect of Fe65 knockdown on cell migration and invasion assessed in trans-well assays. As shown in Fig. 1, Western blot analyses showed that Fe65 shRNA efficiently decreased Fe65 protein in the stable clones (left panels) (full blots available in the Supplementary Information). Compared to control clones, Fe65 knockdown clones exhibited increased migration and invasion in both cell lines (middle panels). Quantitative analyses showed that the increases were significant (right panels). Similar data were obtained from two independent knockdown clones, which excludes the possibility that cloning selection had contributed to the increases in migration and invasion. The above analyses suggest that Fe65 is a suppressor of breast cancer invasion and migration.


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 cell motility in breast cancer cells.(A), 5 × 104 control or Fe65 stable knockdown MDA-MB-231 cells were plated into trans-well inserts and 3% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 8 h after plating. (B), 5 × 104 control or Fe65 stable knockdown MDA-MB-361 cells were plated into trans-well inserts and 5% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 16 h after plating. Western blots show efficient Fe65 knockdown and β-actin blots are included as loading controls. Quantitative data are shown as bar graphs with each data point representing analyses in duplicate performed in parallel that were repeated three times (n = 6). Values are means ± SD. P-values were calculated with student’s t test (1 tailed distribution).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4499803&req=5

f1: Fe65 inhibits cell motility in breast cancer cells.(A), 5 × 104 control or Fe65 stable knockdown MDA-MB-231 cells were plated into trans-well inserts and 3% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 8 h after plating. (B), 5 × 104 control or Fe65 stable knockdown MDA-MB-361 cells were plated into trans-well inserts and 5% FBS was used in the medium at the bottom of 24-well plates to induce the migration and invasion. Cells were fixed and photographed 16 h after plating. Western blots show efficient Fe65 knockdown and β-actin blots are included as loading controls. Quantitative data are shown as bar graphs with each data point representing analyses in duplicate performed in parallel that were repeated three times (n = 6). Values are means ± SD. P-values were calculated with student’s t test (1 tailed distribution).
Mentions: In previous studies, it was noted that Fe65 was expressed at high levels in the cytoplasm of invasive breast cancer cells such as MDA-MB-231 and MDA-MB-36142, suggesting a possible role of Fe65 in controlling breast cancer invasion. To test this, Fe65 stable knockdown clones were established and the effect of Fe65 knockdown on cell migration and invasion assessed in trans-well assays. As shown in Fig. 1, Western blot analyses showed that Fe65 shRNA efficiently decreased Fe65 protein in the stable clones (left panels) (full blots available in the Supplementary Information). Compared to control clones, Fe65 knockdown clones exhibited increased migration and invasion in both cell lines (middle panels). Quantitative analyses showed that the increases were significant (right panels). Similar data were obtained from two independent knockdown clones, which excludes the possibility that cloning selection had contributed to the increases in migration and invasion. The above analyses suggest that Fe65 is a suppressor of breast cancer invasion and migration.

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