Cancer Stem Cell Marker Endoglin (CD105) Induces Epithelial Mesenchymal Transition (EMT) but Not Metastasis in Clear Cell Renal Cell Carcinoma
Junhui Hu
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Search for more papers by this authorWei Guan
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorLibin Yan
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorZhangqun Ye
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorCorresponding Author
Lily Wu
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Search for more papers by this authorCorresponding Author
Hua Xu
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorJunhui Hu
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Search for more papers by this authorWei Guan
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorLibin Yan
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorZhangqun Ye
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorCorresponding Author
Lily Wu
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles CA 90095, USA ucla.edu
Search for more papers by this authorCorresponding Author
Hua Xu
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, China hust.edu.cn
Search for more papers by this authorAbstract
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer. We previously reported that CD105(+) subpopulation in human ccRCC tumors possesses tumor cell self-renewal and chemoresistance capability. In this study, we showed that CD105(+) ACHN tumor cells exhibit epithelial mesenchymal transition (EMT) phenotype with high expression of mesenchymal marker N-cadherin and low expression of epithelial marker E-cadherin. They are more motile and invasive compared to the unselected parental ACHN tumor cells. The knockdown of CD105 by RNA interference led to the downregulation of N-cadherin and the upregulation of E-cadherin and reduced motility and invasiveness of CD105(+) cells. Overexpression of stem cell factor MYC in CD105 knocked down cells increased mesenchymal markers and cell motility. However, the CD105(+) population of tumor cells does not exhibit an increase metastatic potential in vivo. Findings from this study support that CD105 plays a functional role in maintaining cancer stem cell and EMT phenotype, with MYC as a common mediator for both of these traits. Our work suggests that the ability to metastasize does not coincide with the cancer stem cell or EMT function of CD105.
Open Research
Data Availability
All the data used to support the findings of this study are included within the article and supplementary material files.
Supporting Information
| Filename | Description |
|---|---|
| sci9060152-sup-0001-f1.pdfPDF document, 189.5 KB | Supplementary Materials Supplementary Figure S1: schematic organization of cells and transwell inserts in the modified 3D transwell assay. Supplementary Table S1: primer sequences. |
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