MFAP5 promotes basal-like breast cancer progression by activating the EMT program

Yanmei Wu,Wenjin Chen,Ping Wu,Quan Zhang,Xishui Liu,Weiqiang Zheng

doi:10.1186/s13578-019-0284-0

Yanmei Wu, Wenjin Chen + Show 4 more

Open Access

https://doi.org/10.1186/s13578-019-0284-0

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Abstract

PurposeHuman basal-like breast cancer (BLBC) is an aggressive malignancy with poor prognosis. Since most current treatments are ineffective, there is an urgent need to identify therapeutic targets for BLBC. Microfibrillar-associated protein 5 (MFAP5) plays an important role in the integration of elastic microfibers and the regulation of endothelial cell behaviors. We previously demonstrated that MFAP5 was significantly overexpressed in BLBC tissues and associated with poor metastasis-free survival of patients with BLBC. However, the detailed role of MFAP5 in BLBC is unclear. Thereby, the current study aimed to investigate the underlying function of MFAP5 in BLBC.MethodFunctional analyses were conducted for the role of MFAP5 in BLBC in vitro and in vivo.ResultsOverexpression of MFAP5 resulted in a significant increase in the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) markers in BLBC in vitro and in vivo. In addition, other metastasis animal models by tail intravenous injection of BT20 cells further confirmed that MFAP5 overexpression promoted BLBC proliferation and BT20 cells metastasis. We found that the TGF-β or Notch inhibitor significantly reversed the tumorigenicity and metastasis of MFAP5-induced BLBC cells.ConclusionOur findings suggest that MFAP5 may promote EMT in BLBC metastasis via the TGF-β/Notch pathway.

Highlights

Breast cancer is the second leading cause of cancer for women mortality worldwide [1]
Overexpression of Microfibrillarassociated protein 5 (MFAP5) resulted in a significant increase in the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) markers in basallike breast cancer (BLBC) in vitro and in vivo
Other metastasis animal models by tail intravenous injection of BT20 cells further confirmed that MFAP5 overexpression promoted BLBC proliferation and BT20 cells metastasis

Summary

Introduction

Breast cancer is the second leading cause of cancer for women mortality worldwide [1]. According to gene expression profiling, it can be classified into four major molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and human basallike breast cancer (BLBC) [1]. BLBC has low expression of the estrogen receptor (ER), progesterone receptor (PR) and HER2 gene, while the expression of basal cytokeratins (CK5/6, CK14, and CK17), epidermal growth factor receptor (EGFR), c-kit and p53 are transcriptionally. Utilizing additional immunohistochemistry (IHC) markers such as basal cytokeratins and EGFR have proven to be better in defining BLBC than triple-negative phenotype, but the disadvantage is the lacking of accuracy [9, 10]. More and more evidences have shown that Notch overexpression is strongly associated with breast cancer invasion, which is an important factor in maintaining the malignant phenotype of breast cancer stem cells [16]. Notchl signaling correlates with self-renewal and differentiation of breast cancer stem cells (CSCs) and their malignant behaviors [17]

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