Wu Yanmei, Wu Ping, Zhang Quan, Chen Wenjin, Liu Xishui, Zheng Weiqiang
1Department of Breast Surgery, Changhai Hospital, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433 China.
Department of Pathology, Maternal and Child Health Care Hospital, Huaian, 223002 Jiangsu China.
Cell Biosci. 2019 Mar 7;9:24. doi: 10.1186/s13578-019-0284-0. eCollection 2019.
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.
Functional analyses were conducted for the role of MFAP5 in BLBC in vitro and in vivo.
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.
Our findings suggest that MFAP5 may promote EMT in BLBC metastasis via the TGF-β/Notch pathway.
人基底样乳腺癌（BLBC）是一种侵袭性恶性肿瘤，预后较差。由于目前大多数治疗方法无效，因此迫切需要确定BLBC的治疗靶点。微纤维相关蛋白5（MFAP5）在弹性微纤维的整合和内皮细胞行为的调节中起重要作用。我们之前证明MFAP5在BLBC组织中显著过表达，且与BLBC患者无转移生存期差相关。然而，MFAP5在BLBC中的具体作用尚不清楚。因此，本研究旨在探讨MFAP5在BLBC中的潜在功能。
对MFAP5在BLBC中的作用进行体内和体外功能分析。
MFAP5的过表达导致BLBC在体内和体外的增殖、迁移、侵袭及上皮-间质转化（EMT）标志物显著增加。此外，通过尾静脉注射BT20细胞建立的其他转移动物模型进一步证实，MFAP5过表达促进BLBC增殖和BT20细胞转移。我们发现，TGF-β或Notch抑制剂可显著逆转MFAP5诱导的BLBC细胞的致瘤性和转移。
我们的研究结果表明，MFAP5可能通过TGF-β/Notch途径促进BLBC转移中的EMT。
