Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma.

ABSTRACT: Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing (VHL⁺) cells. Renal tumors with either VHL⁺ or VHL-KO cells alone exhibit minimal metastatic potential. Combined tumors displayed r

SUBMITTER: Hu J 

PROVIDER: S-EPMC10110583 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature