hMAGEA2 promotes progression of breast cancer by regulating Akt and Erk1/2 pathways

Abstract

Breast cancer is the most abundant cancer worldwide and a severe problem for women. Notably, breast cancer has a high mortality rate, mainly because of tumor progression and metastasis. Triple-negative breast cancer (TNBC) is highly progressive and lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Therefore, there are no established therapeutic targets against TNBC. In this study, we investigated whether the expression of human melanoma-associated antigen A2 (MAGEA2) is associated with TNBC. We found that hMAGEA2 is significantly overexpressed in human TNBC tissues; we also observed oncogenic properties using TNBC cell lines (MDA-MB-231 and MDA-MB-468). The overexpression of hMAGEA2 in MDA-MB-231 cell line showed dramatically increased cellular proliferation, colony formation, invasion, and xenograft tumor formation and growth. Conversely, knockdown of hMAEGA2 in MDA-MB-468 cell line suppressed cellular proliferation, colony formation, and xenograft tumor formation. Additionally, we showed that hMAGEA2 regulated the activation of Akt and Erk1/2 signaling pathways. These data indicate that hMAGEA2 is important for progression of TNBC and may serve as a novel molecular therapeutic target.

Transcriptome sequencing to detect the potential role of long non-coding RNAs in bovine mammary gland during the dry and lactation period

“…3a , 69 significantly enriched GO terms ( P < 0.05) were identified, such as negative regulation of cell growth (GO: 0030308), growth factor activity (GO: 0008083), positive regulations of ERK1 and ERK2 cascade (GO: 0070374), and sodium channel complex (GO: 0034706), etc. ERK1 and ERK2 had been suggested to play an important role in regulating cell invasion, cell proliferation, and colony formation in triple-negative breast cancer cell lines [ 39 ]. Growth factors, especially the epidermal growth factors (EGFs) and insulin-like growth factors (IGFs), were involved in development of normal mammary gland and pathogenesis of breast cancer [ 40 ].…”

Jazf1 promotes prostate cancer progression by activating JNK/Slug

“…Overexpression cell lines exhibited increased cell proliferation compared to empty vector cell lines. In addition, colony formation ability, one of cancer’s main characteristics, was enhanced in Jazf1-overexpressing cell lines [ 29 – 31 ]. Similarly, we established DU145 cell lines with Jazf1 knock-down using shRNA infection.…”

Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells

“…First, MAGEA2 was predicted to exert its influence through the Erk1/2 signaling pathway because a previous study reported the role of human MAGEA2 in regulating the Erk1/2 signaling pathway in breast cancer. 30 Second, a decrease in MAGEA2 expression was predicted to reduce the phosphorylation of Stat3 because it is known that the Stat3 signaling pathway plays a crucial role in maintaining the pluripotency of mESCs. 31 The final prediction was that MAGEA2 may influence both the Erk1/2 and Stat3 signaling pathways.…”

“…This is consistent with the findings from numerous previous studies regarding the correlation between MAGEA2 expression and various types of cancer, which reported that cell proliferation was reduced concomitant with decreased MAGEA2 expression. 30,[32][33][34] To examine the potential causes for the reduced mESC proliferation, we evaluated two essential factors associated with the regulation of proliferation: cell cycle and apoptosis. Analysis of the cell cycle using flow cytometry detected S phase arrest and significantly reduced expression of Cdk2 and Cyclin A1, the proteins activated during the transition from the S phase to the G2/M phase.…”