Cancer Stem Cell Marker Endoglin (CD105) Induces Epithelial Mesenchymal Transition (EMT) but Not Metastasis in Clear Cell Renal Cell Carcinoma

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.