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

Abstract

Purpose Human 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. Method Functional analyses were conducted for the role of MFAP5 in BLBC in vitro and in vivo. Results Overexpression 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. Conclusion Our findings suggest that MFAP5 may promote EMT in BLBC metastasis via the TGF-β/Notch pathway. Electronic supplementary material The online version of this article (10.1186/s13578-019-0284-0) contains supplementary material, which is available to authorized users.

Prognostic and clinicopathological values of tissue expression of MFAP5 and ITM2A in triple-negative breast cancer: an immunohistochemical study

“…We found that MFAP5 tissue expression in TNBC cells was associated with unfavourable pathological data and dismal outcome, similarly to previous studies [ 1 , 13 – 15 ].…”

“…TNBC, which is a molecular subtype of breast cancer, has aggressive behaviour, no targeted therapy, and high incidence of disease progression and development of metastases; hence, it needs further evaluation and new studies to detect novel prognostic markers and targeted therapy to improve its outcome [ 1 ]. EMT initiation and activation in tumour cells is thought to be responsible for starting and maintaining the metastatic program [ 12 ].…”

“…Triple-negative breast cancer (TNBC) is an aggressive molecular subtype of breast cancer and is characterised by negative oestrogen receptor (OR), progesterone receptor (PR), and HER2-neu [ 1 ]. It has an aggressive behaviour and unfavourable prognostic criteria such as high grade, early brain and lung metastasis, dismal outcome, and unfavourable survival rates [ 2 ].…”

“…There is a plethora of signalling pathways that are incriminated in the activation of EMT [ 5 ]. Microfibrillar-associated protein 5 (MFAP5) is a protein with multiple functions, which plays an essential role in the regulation of cell behaviour and survival [ 1 ]. MFAP5 is one of the expressed genes in most human malignancies; a few studies have clarified its function [ 6 ].…”

Molecular structure and function of microfibrillar‐associated proteins in skeletal and metabolic disorders and cancers

“…MFAP5 has been indicated as a potential biomarker for predicting the prognosis of tongue carcinoma (X. Yang et al, 2017), and in duct carcinoma in situ (Dawoud, Abouelfadl, Abdou, & Elkhouly, 2018). In addition, it was suggested to be associated with in the progression of cervical cancer (Q. Li, Zhang, & Jiang, 2018), patient survival of oral tongue squamous cell carcinoma (Principe et al, 2018), and in human basal‐like breast cancer (Y. Wu et al, 2019). However, further evaluation of MFAP5 as a specific cancer biomarker is required.…”