期刊
ONCOTARGET
卷 6, 期 8, 页码 5567-5581出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1901
关键词
Clear cell renal cell carcinoma; microRNA; Cancer stem cell- Tumor initiating cell; Epithelial-to-mesenchymal transition
资金
- Canadian Cancer Society (CCS) [20185]
- Canadian Institute of Health Research [MOP119606]
- Kidney Foundation of Canada
- Prostate Cancer Canada
Renal cell carcinoma (RCC) is an aggressive disease, with 35% chance of metastasis. The 'cancer stem cell' hypothesis suggests that a subset of cancer cells possess stem cell properties and is crucial in tumor initiation, metastasis and treatment resistance. We isolated RCC spheres and showed that they exhibit cancer stem cell/ tumor initiating cell-like properties including the formation of self-renewing spheres, high tumorigenicity and the ability to differentiate to cell types of the original tumor. Spheres showed increased expression of stem cell-related transcription factors and mesenchymal markers. miRNAs were differentially expressed between RCC spheres and their parental cells. Inhibition of miR-17 accelerated the formation of RCC spheres which shared molecular characteristics with the spontaneous RCC spheres. Target prediction pointed out TGF beta pathway activation as a possible mechanism to drive RCC sphere formation. We demonstrate that miR-17 overexpression interferes with the TGF beta-EMT axis and hinders RCC sphere formation; and validated TGFBR2 as a direct and biologically relevant target during this process. Thus, a single miRNA may have an impact on the formation of highly tumorigenic cancer spheres of kidney cancer.
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