• Junhui Hu, Wei Guan, Peijun Liu, Jin Dai, Kun Tang, Haibing Xiao, Yuan Qian, Allison C Sharrow, Zhangqun Ye, Lily Wu, and Hua Xu.
• Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China; Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
• Stem Cell Reports. 2017 Aug 8; 9 (2): 464-477.

AbstractRenal cell carcinoma (RCC) is a deadly malignancy due to its tendency to metastasize and resistance to chemotherapy. Stem-like tumor cells often confer these aggressive behaviors. We discovered an endoglin (CD105)-expressing subpopulation in human RCC xenografts and patient samples with a greater capability to form spheres in vitro and tumors in mice at low dilutions than parental cells. Knockdown of CD105 by short hairpin RNA and CRISPR/cas9 reduced stemness markers and sphere-formation ability while accelerating senescence in vitro. Importantly, downregulation of CD105 significantly decreased the tumorigenicity and gemcitabine resistance. This loss of stem-like properties can be rescued by CDA, MYC, or NANOG, and CDA might act as a demethylase maintaining MYC and NANOG. In this study, we showed that Endoglin (CD105) expression not only demarcates a cancer stem cell subpopulation but also confers self-renewal ability and contributes to chemoresistance in RCC.Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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