2. Academic Validation
  3. TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer

TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer

  • Nat Commun. 2021 Jul 20;12(1):4413. doi: 10.1038/s41467-021-24703-7.
Jiahui Xu 1,  Xiaoli Yang 1,  Qiaodan Deng 1,  Cong Yang 2,  Dong Wang 3,  Guojuan Jiang 1,  Xiaohong Yao 4,  Xueyan He 1,  Jiajun Ding 1,  Jiankun Qiang 1,  Juchuanli Tu 1,  Rui Zhang 1,  Qun-Ying Lei 1,  Zhi-Min Shao 1,  Xiuwu Bian 5,  Ronggui Hu 6,  Lixing Zhang 7,  Suling Liu 8
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College, Fudan University, Shanghai, China.
  • 2 School of Medicine, Guizhou University, Guiyang, Guizhou, China.
  • 3 WPI Nano Life Science Institute, Kanazawa University, Kakuma-machi, Kanazawa, Japan.
  • 4 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University); Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • 5 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University); Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China. bianxiuwu@263.net.
  • 6 State Key Laboratory of Molecular Biology; CAS Center for Excellence in Molecular Cell Science; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. coryhu00@gmail.com.
  • 7 Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College, Fudan University, Shanghai, China. zhang_lx@fudan.edu.cn.
  • 8 Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College, Fudan University, Shanghai, China. suling@fudan.edu.cn.
PMID: 34285210 DOI: 10.1038/s41467-021-24703-7
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.

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