Limits...
The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.

Dong H, Guo H, Xie L, Wang G, Zhong X, Khoury T, Tan D, Zhang H - PLoS ONE (2013)

Bottom Line: The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer.MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential.Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China.

ABSTRACT
Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

Show MeSH

Related in: MedlinePlus

Immunohistochemical staining for MTA3, Snail, and E-cadherin in GEJ adenocarcinoma and adjacent noncancerous tissue.Representative samples of noncancerous tissue, well differentiated tumor and poorly differentiated tumor are shown. Strong to negative staining for MTA3 (top). Negative to strong staining for Snail (middle). Strong to weak staining for E-cadherin (bottom). The arrow indicates perinuclear staining of Snail. The dotted insert showed strongly positive staining for MTA3 in breast cancer cells as positive control (original magnification 400×).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3643958&req=5

pone-0062986-g002: Immunohistochemical staining for MTA3, Snail, and E-cadherin in GEJ adenocarcinoma and adjacent noncancerous tissue.Representative samples of noncancerous tissue, well differentiated tumor and poorly differentiated tumor are shown. Strong to negative staining for MTA3 (top). Negative to strong staining for Snail (middle). Strong to weak staining for E-cadherin (bottom). The arrow indicates perinuclear staining of Snail. The dotted insert showed strongly positive staining for MTA3 in breast cancer cells as positive control (original magnification 400×).

Mentions: MTA3 has been recognized as a master inhibitor of EMT in cancer, which inhibits Snail to increase E-cadherin expression. To obtain the functional insight into MTA3 in EMT and tumor progression of GEJ adenocarcinoma, we characterized the expression profile of MTA3-pathway components in GEJ adenocarcinoma. Protein expression of MTA3, Snail and E-cadherin was assayed in a cohort of 128 primary GEJ adenocarcinoma. In total examined specimens, positive immunostaining for MTA3 was observed in both the nucleus and the cytoplasm of neoplastic cells in 63 (49.2%), whereas strong MTA3 immunoreactivity was predominantly found in the nuclei of epithelial cells in noncancerous tissues (Figure 2; top). Human breast cancer samples served as a positive control for MTA3 immunoreactivity (dotted insert in Figure 2). Tumor cells in 87 (68%) of the specimens exhibited strong cytoplasmic staining for Snail; in contrast, there was an absence of staining for Snail in all the noncancerous epithelial cells (Figure 2; middle). Perinuclear staining was frequently observed in Snail-positive cells (arrows in Figure 2). In contrast to the noncancerous epithelial cells, which exhibited strong E-cadherin immunostaining, decreased membrane staining for E-cadherin was observed in tumor cells in 73 (57%) of the specimens (Figure 2; bottom). Taken together, these observations clearly suggest that MTA3-regulated EMT pathway is altered in GEJ adenocarcinoma.


The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.

Dong H, Guo H, Xie L, Wang G, Zhong X, Khoury T, Tan D, Zhang H - PLoS ONE (2013)

Immunohistochemical staining for MTA3, Snail, and E-cadherin in GEJ adenocarcinoma and adjacent noncancerous tissue.Representative samples of noncancerous tissue, well differentiated tumor and poorly differentiated tumor are shown. Strong to negative staining for MTA3 (top). Negative to strong staining for Snail (middle). Strong to weak staining for E-cadherin (bottom). The arrow indicates perinuclear staining of Snail. The dotted insert showed strongly positive staining for MTA3 in breast cancer cells as positive control (original magnification 400×).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643958&req=5

pone-0062986-g002: Immunohistochemical staining for MTA3, Snail, and E-cadherin in GEJ adenocarcinoma and adjacent noncancerous tissue.Representative samples of noncancerous tissue, well differentiated tumor and poorly differentiated tumor are shown. Strong to negative staining for MTA3 (top). Negative to strong staining for Snail (middle). Strong to weak staining for E-cadherin (bottom). The arrow indicates perinuclear staining of Snail. The dotted insert showed strongly positive staining for MTA3 in breast cancer cells as positive control (original magnification 400×).
Mentions: MTA3 has been recognized as a master inhibitor of EMT in cancer, which inhibits Snail to increase E-cadherin expression. To obtain the functional insight into MTA3 in EMT and tumor progression of GEJ adenocarcinoma, we characterized the expression profile of MTA3-pathway components in GEJ adenocarcinoma. Protein expression of MTA3, Snail and E-cadherin was assayed in a cohort of 128 primary GEJ adenocarcinoma. In total examined specimens, positive immunostaining for MTA3 was observed in both the nucleus and the cytoplasm of neoplastic cells in 63 (49.2%), whereas strong MTA3 immunoreactivity was predominantly found in the nuclei of epithelial cells in noncancerous tissues (Figure 2; top). Human breast cancer samples served as a positive control for MTA3 immunoreactivity (dotted insert in Figure 2). Tumor cells in 87 (68%) of the specimens exhibited strong cytoplasmic staining for Snail; in contrast, there was an absence of staining for Snail in all the noncancerous epithelial cells (Figure 2; middle). Perinuclear staining was frequently observed in Snail-positive cells (arrows in Figure 2). In contrast to the noncancerous epithelial cells, which exhibited strong E-cadherin immunostaining, decreased membrane staining for E-cadherin was observed in tumor cells in 73 (57%) of the specimens (Figure 2; bottom). Taken together, these observations clearly suggest that MTA3-regulated EMT pathway is altered in GEJ adenocarcinoma.

Bottom Line: The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer.MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential.Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China.

ABSTRACT
Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

Show MeSH
Related in: MedlinePlus