Endoglin Is Essential for the Maintenance of Self-Renewal and Chemoresistance in Renal Cancer Stem Cells

• DOI: 10.1016/j.stemcr.2017.07.009
• Publication Date: 2017-08-08T20:07:06Z
• Authors: Junhui Hu; Wei Guan; Peijun Liu; Jin Dai; Kun Tang; Haibing Xiao; Yuan Qian; Allison C. Sharrow; Zhangqun Ye; Lily Wu; Hua Xu
• Keywords: Male; 0301 basic medicine; Medicine (General); Kidney Disease; Drug Resistance; Genes, myc; Cell Transformation; Mice; Stem Cell Research - Nonembryonic - Human; Biology (General); Cell Self Renewal; Cellular Senescence; Cancer; cytidine deaminase; endoglin; Tumor; Endoglin; kidney cancer; Nanog Homeobox Protein; Biological Sciences; myc; Kidney Neoplasms; 3. Good health; Cell Transformation, Neoplastic; Gene Knockdown Techniques; Neoplastic Stem Cells; Stem Cell Research - Nonembryonic - Non-Human; cancer stem cell; QH301-705.5; Cell Survival; Clinical Sciences; 610; Antineoplastic Agents; Article; Cell Line; 03 medical and health sciences; Rare Diseases; R5-920; Cell Line, Tumor; Genetics; Animals; Humans; Cell Proliferation; Neoplastic; Animal; demethylation; Stem Cell Research; Xenograft Model Antitumor Assays; Disease Models, Animal; Orphan Drug; Genes; Drug Resistance, Neoplasm; Biochemistry and cell biology; Disease Models; Neoplasm; Biochemistry and Cell Biology; Biomarkers

Renal 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.