Limits...
AurkA controls self-renewal of breast cancer-initiating cells promoting wnt3a stabilization through suppression of miR-128.

Eterno V, Zambelli A, Villani L, Tuscano A, Manera S, Spitaleri A, Pavesi L, Amato A - Sci Rep (2016)

Bottom Line: In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells.As a consequence, the amount of BCICs and their migratory capability dramatically decreased.In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

View Article: PubMed Central - PubMed

Affiliation: Lab of Experimental Oncology &Pharmacogenomics IRCCS Fondazione "Salvatore Maugeri", Pavia, Italy.

ABSTRACT
AurkA overexpression was previously found in breast cancer and associated to its ability in controlling chromosome segregation during mitosis, however whether it may affect breast cancer cells, endorsed with stem properties (BCICs), is still unclear. Surprisingly, a strong correlation between AurkA expression and β-catenin localization in breast cancer tissues suggested a link between AurkA and Wnt signaling. In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells. As a consequence, the amount of BCICs and their migratory capability dramatically decreased. Conversely, wnt3a mRNA stabilization and increased CD44(+)/CD24(low/-) subpopulation was found in AurkA-overexpressing MCF7 cells. In vivo, AurkA-overexpressing primary breast cancer cells showed higher tumorigenic properties. Interestingly, we found that AurkA suppressed the expression of miR-128, inhibitor of wnt3a mRNA stabilization. Namely, miR-128 suppression realized after AurkA binding to Snail. Remarkably, a strong correlation between AurkA and miR-128 expression in breast cancer tissues confirmed our findings. This study provides novel insights into an undisclosed role for the kinase AurkA in self-renewal and migration of BCICs affecting response to cancer therapies, metastatic spread and recurrence. In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

No MeSH data available.


Related in: MedlinePlus

Aurka overexpression is associated with β-catenin nuclear/cytoplasmic localization.(A) Representative images of AurkA or β-catenin staining in 10 breast cancer tissues (HS2, HS4, HS6, HS7, HS9, HS14, HS15, HS18, HS20, HS21). Magnification 400X. Representative images of a normal breast tissue at 200X or 400X magnification were showed as controls (NBr 200X and NBr 400X). Nuclei were counterstained with Hematoxylin. B) Relative expression of AurkA (black bars) and CD44 (grey bars) in 32 breast cancer tissues (HS1-32). AurkA and CD44 fold changes result after normalization with normal breast tissue (N-Br). Data results from triplicate (±standard error) of each sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4920028&req=5

f1: Aurka overexpression is associated with β-catenin nuclear/cytoplasmic localization.(A) Representative images of AurkA or β-catenin staining in 10 breast cancer tissues (HS2, HS4, HS6, HS7, HS9, HS14, HS15, HS18, HS20, HS21). Magnification 400X. Representative images of a normal breast tissue at 200X or 400X magnification were showed as controls (NBr 200X and NBr 400X). Nuclei were counterstained with Hematoxylin. B) Relative expression of AurkA (black bars) and CD44 (grey bars) in 32 breast cancer tissues (HS1-32). AurkA and CD44 fold changes result after normalization with normal breast tissue (N-Br). Data results from triplicate (±standard error) of each sample.

Mentions: We analyzed the expression of AurkA kinase in 89 breast cancer patients by immunohistochemistry (IHC) (Fig. 1A). A significant positive staining of the kinase was found in 41 out 89 breast cancer patients (46.07%). However no correlation was found between AurkA overexpression and clinical and pathological features as grading (Pvalue = 0.759), Ki67 (Pvalue = 0.574), tumor size (Pvalue = 0.553) or linfonodal status (Pvalue = 0.107) in N = 89 breast cancer samples (Table 1).


AurkA controls self-renewal of breast cancer-initiating cells promoting wnt3a stabilization through suppression of miR-128.

Eterno V, Zambelli A, Villani L, Tuscano A, Manera S, Spitaleri A, Pavesi L, Amato A - Sci Rep (2016)

Aurka overexpression is associated with β-catenin nuclear/cytoplasmic localization.(A) Representative images of AurkA or β-catenin staining in 10 breast cancer tissues (HS2, HS4, HS6, HS7, HS9, HS14, HS15, HS18, HS20, HS21). Magnification 400X. Representative images of a normal breast tissue at 200X or 400X magnification were showed as controls (NBr 200X and NBr 400X). Nuclei were counterstained with Hematoxylin. B) Relative expression of AurkA (black bars) and CD44 (grey bars) in 32 breast cancer tissues (HS1-32). AurkA and CD44 fold changes result after normalization with normal breast tissue (N-Br). Data results from triplicate (±standard error) of each sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920028&req=5

f1: Aurka overexpression is associated with β-catenin nuclear/cytoplasmic localization.(A) Representative images of AurkA or β-catenin staining in 10 breast cancer tissues (HS2, HS4, HS6, HS7, HS9, HS14, HS15, HS18, HS20, HS21). Magnification 400X. Representative images of a normal breast tissue at 200X or 400X magnification were showed as controls (NBr 200X and NBr 400X). Nuclei were counterstained with Hematoxylin. B) Relative expression of AurkA (black bars) and CD44 (grey bars) in 32 breast cancer tissues (HS1-32). AurkA and CD44 fold changes result after normalization with normal breast tissue (N-Br). Data results from triplicate (±standard error) of each sample.
Mentions: We analyzed the expression of AurkA kinase in 89 breast cancer patients by immunohistochemistry (IHC) (Fig. 1A). A significant positive staining of the kinase was found in 41 out 89 breast cancer patients (46.07%). However no correlation was found between AurkA overexpression and clinical and pathological features as grading (Pvalue = 0.759), Ki67 (Pvalue = 0.574), tumor size (Pvalue = 0.553) or linfonodal status (Pvalue = 0.107) in N = 89 breast cancer samples (Table 1).

Bottom Line: In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells.As a consequence, the amount of BCICs and their migratory capability dramatically decreased.In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

View Article: PubMed Central - PubMed

Affiliation: Lab of Experimental Oncology &Pharmacogenomics IRCCS Fondazione "Salvatore Maugeri", Pavia, Italy.

ABSTRACT
AurkA overexpression was previously found in breast cancer and associated to its ability in controlling chromosome segregation during mitosis, however whether it may affect breast cancer cells, endorsed with stem properties (BCICs), is still unclear. Surprisingly, a strong correlation between AurkA expression and β-catenin localization in breast cancer tissues suggested a link between AurkA and Wnt signaling. In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells. As a consequence, the amount of BCICs and their migratory capability dramatically decreased. Conversely, wnt3a mRNA stabilization and increased CD44(+)/CD24(low/-) subpopulation was found in AurkA-overexpressing MCF7 cells. In vivo, AurkA-overexpressing primary breast cancer cells showed higher tumorigenic properties. Interestingly, we found that AurkA suppressed the expression of miR-128, inhibitor of wnt3a mRNA stabilization. Namely, miR-128 suppression realized after AurkA binding to Snail. Remarkably, a strong correlation between AurkA and miR-128 expression in breast cancer tissues confirmed our findings. This study provides novel insights into an undisclosed role for the kinase AurkA in self-renewal and migration of BCICs affecting response to cancer therapies, metastatic spread and recurrence. In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

No MeSH data available.


Related in: MedlinePlus