1. TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer
- Author
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Xiaoli Yang, Suling Liu, Jiahui Xu, Xiaohong Yao, Xiu-Wu Bian, Qiaodan Deng, Jiankun Qiang, Xueyan He, Dong Wang, Lixing Zhang, Guojuan Jiang, Jiajun Ding, Cong Yang, Zhi-min Shao, Juchuanli Tu, Ronggui Hu, Qun-Ying Lei, and Rui Zhang
- Subjects
0301 basic medicine ,Carcinogenesis ,Science ,Population ,RhoC ,General Physics and Astronomy ,Estrogen receptor ,Antineoplastic Agents ,Receptors, Cell Surface ,Triple Negative Breast Neoplasms ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Breast cancer ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Vasculogenic mimicry ,Breast ,Cell Self Renewal ,education ,skin and connective tissue diseases ,Triple-negative breast cancer ,Mastectomy ,education.field_of_study ,Multidisciplinary ,biology ,Neovascularization, Pathologic ,Cancer stem cells ,Microfilament Proteins ,General Chemistry ,Middle Aged ,medicine.disease ,Xenograft Model Antitumor Assays ,Ubiquitin ligase ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Neoplastic Stem Cells ,Female - Abstract
Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously., Vasculogenic mimicry (VM) contributes to the development of triple-negative breast cancer. In this study, the authors show that TEM8 is expressed in VM-forming breast cancer stem cells and it promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis
- Published
- 2021