HMAGEA2 promotes progression of breast cancer by regulating Akt and Erk1/2 pathways.

Song Park,Myoung Ok Kim,Si Jun Park,Zae Young Ryoo,Wookbong Kwon,Dong Joon Kim,Jinhee Lee,Soyoung Jang,Sung-Hyun Kim,Minjee Choi,Jain Jeong,Kangdong Liu,Hyeng-Soo Kim,Zigang Dong,Mee-Hyun Lee,Yonghun Sung

doi:10.18632/oncotarget.16184

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.

Highlights

Triple-negative breast cancer (TNBC), which accounts for approximately 15% of breast cancer in women, is defined by lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [1,2,3,4]
Lymph node metastasis is associated with high levels of extracellular signaling-related kinase (ERK) [17], www.impactjournals.com/oncotarget while mitogen-activated protein kinase (MAPK) activation in TNBC is linked with a higher rate of recurrence [18], indicating that the Akt and ERK signaling pathways play an important role in progression of TNBC
Our results showed that the expression of human melanoma-associated antigen A2 (hMAGEA2) was significantly upregulated in human TNBC and breast cancer tissues compared with human precancer tissues (Figure 1A, 1B)

Summary

Introduction

Triple-negative breast cancer (TNBC), which accounts for approximately 15% of breast cancer in women, is defined by lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [1,2,3,4]. Breast cancer is strongly influenced by dysregulation of the Akt and mitogen-activated protein kinase (MAPK) signaling cascades. Extracellular signaling-related kinase (ERK), a member of the MAPK pathway, is expressed at higher levels in TNBC [15]; ERK plays a critical role in cell proliferation and differentiation, promotes epithelial-mesenchymal transition (EMT), and accelerates cell migration by affecting contact between cells and the extracellular matrix (ETM) [6, 8, 16]. Lymph node metastasis is associated with high levels of ERK [17], www.impactjournals.com/oncotarget while MAPK activation in TNBC is linked with a higher rate of recurrence [18], indicating that the Akt and ERK signaling pathways play an important role in progression of TNBC

Methods

Results

Conclusion