机构:[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China普通外科[2]School of Basic Medical Sciences, Capital Medical University, Beijing, China
The tumor microenvironment (TME) regulates tumor progression, and cancer-associated fibroblasts (CAFs) are the primary stromal components of the TME, with the potential to drive tumor metastasis via the secretion of paracrine factors, but the specific mechanisms driving this process have not been defined.
Proteins secreted from CAFs and normal fibroblasts (NFs) were analyzed via proteomic analysis (fold change >?2, p?<?0.05) to identify tumor-promoting proteins secreted by CAFs.
Proteomic analysis revealed that microfibrillar-associated protein 5 (MFAP5) is preferentially expressed and secreted by CAFs relative to NFs, which was confirmed by Western blotting and RT-qPCR. Transwell and wound healing assays confirmed that MFAP5 is secreted by CAFs, and drives the invasion and migration of MCF7 breast cancer cells. We further found that in MCF7 cells MFAP5 promoted epithelial-mesenchymal transition, activating Notch1 signaling and consequently upregulating NICD1 and slug. When Notch1 was knocked down in MCF7 cells, the ability of MFAP5 to promote invasion and migration decreased.
CAFs promote cancer cells invasion and migration via MFAP5 secretion and activation of the Notch1/slug signaling. These data highlight this pathway as a therapeutic target to disrupt tumor progression through the interference of CAF-tumor crosstalk.
基金:
国家自然科学基金
语种:
外文
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2018]版:
大类|3 区医学
小类|4 区肿瘤学
最新[2023]版:
大类|3 区医学
小类|4 区肿瘤学
第一作者:
第一作者机构:[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
通讯作者:
通讯机构:[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714):
Chen Z,Yan X,Li K,et al.Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling.[J].CLINICAL & TRANSLATIONAL ONCOLOGY.2019,doi:10.1007/s12094-019-02156-1.
APA:
Chen Z,Yan X,Li K,Ling Y&Kang H.(2019).Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling..CLINICAL & TRANSLATIONAL ONCOLOGY,,
MLA:
Chen Z,et al."Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling.".CLINICAL & TRANSLATIONAL ONCOLOGY .(2019)