MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Abstract

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.59%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of β-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and β-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.

Expression of MAGE‐A and NY‐ESO‐1 cancer/testis antigens is enriched in triple‐negative invasive breast cancers

“…We investigated the expression of MAGE‐A and NY‐ESO‐1 in invasive breast cancer, and found prevalent expression within the TN group. Previous reports have shown variable expression of MAGE‐A and NY‐ESO‐1, ranging between 17% and 74%, and between 2% and 40%, respectively, and the expression levels of both were higher in TNBC, which corroborates our findings. Taking advantage of the large pre‐existing dataset on experimental biomarkers in the QFU cohort, we found that the CTAs are expressed most prevalently in the TN tumours showing salient features of poor differentiation/primitive phenotype, proliferation, and genomic instability.…”

TNFAIP3 inhibits migration and invasion in nasopharyngeal carcinoma by suppressing epithelial mesenchymal transition

“…EMT, a key promoting factor for cancer invasion and migration, results in the downregula-tion of epithelial marker and upregulation of mesenchymal markers toward mesenchymal phenotype [17][18][19]. Mounting evidence suggests that EMT is a vital prerequisite for invasion and migration in various cancer [18,[20][21][22]. In the present study, epithelial marker E-cadherin was found to be upregulated, whereas mesenchymal marker vimentin was downregulated in TNFAIP3-overexpressing cells.…”

“…We further provide data indicating that knockdown of TNFAIP3 significantly stimulated migration and invasion, whereas TNFAIP3 overexpression inhibited migration and invasion in NPC cells. EMT, a key promoting factor for cancer invasion and migration, results in the downregula-tion of epithelial marker and upregulation of mesenchymal markers toward mesenchymal phenotype [17][18][19]. Mounting evidence suggests that EMT is a vital prerequisite for invasion and migration in various cancer [18,[20][21][22].…”

Tumor suppressor let-7a inhibits breast cancer cell proliferation, migration and invasion by targeting MAGE-A1

“…MAGE-A family members are highly expressed in cancers and play critical roles in tumorigenesis [26]. MAGE-A1, a member of the let-7 family, is abnormally expressed in several types of tumors, including breast [17][18]27], colorectal [28] and bladder cancers [29] and also glioma [30]. Our group reported that MAGE-A's are not expressed in breast cancer adjacent tissues and that the positivity rate in breast cancer tissues was 49.17%.…”

“…Our group reported that MAGE-A's are not expressed in breast cancer adjacent tissues and that the positivity rate in breast cancer tissues was 49.17%. Their expression is associated with a high histological grade and axillary lymph node metastasis, and MAGE-A expression is significantly higher in TNBC and may be responsible for its high aggressiveness and epithelial mesenchymal transition (EMT) [27].…”