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Updated: May 10, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Identification of pVHL as a novel substrate for Aurora-A in clear cell renal cell carcinoma (ccRCC)
Benedicte Martin1, Franck Chesnel, Jean-Guy Delcros
1CNRS - UMR 6290 (IGDR) -Université Rennes 1- BIOSIT - Rennes, France.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is often characterized by mutations or deletions of the Von Hippel Lindau (VHL) tumour suppressor gene. Aurora gene family members are implicated in proper mitotic progression and spindle checkpoint function and play a crucial role in cancer progression. In the present study, we assessed the expression of Aurora-A in a cohort of 30 ccRCC with fully characterized VHL status (wt/wt or mut/del) and Fuhrman grade. Aurora-A transcript and protein levels were significantly increased in high Fuhrman grade tumours and in VHLwt/wt tumours. These results suggest that Aurora-A and VHL interact in the ccRCC. We demonstrated that the two proteins interact in vivo and identified the Ser72 on the sequence of VHL as the unique site phosphorylated by Aurora-A.
Insights
Clear cell renal cell carcinoma (ccRCC) shows increased Aurora-A in high-grade tumors and VHL wild-type status. Aurora-A and the Von Hippel Lindau (VHL) protein interact, with Aurora-A phosphorylating VHL at Ser72.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype.
- Mutations or deletions in the Von Hippel Lindau (VHL) gene are frequent in ccRCC.
- Aurora gene family members are crucial for cell division and cancer progression.
Purpose of the Study:
- To investigate the expression of Aurora-A in ccRCC.
- To explore the relationship between Aurora-A, VHL status, and tumor grade.
- To determine if Aurora-A and VHL interact in ccRCC.
Main Methods:
- Assessed Aurora-A transcript and protein levels in 30 ccRCC tumors.
- Characterized VHL status (wild-type/mutant/deleted) and Fuhrman grade for all tumors.
- Performed in vivo interaction studies between Aurora-A and VHL.
Main Results:
- Aurora-A transcript and protein levels were significantly elevated in high Fuhrman grade ccRCC tumors.
- Higher Aurora-A expression was observed in tumors with wild-type VHL (VHLwt/wt).
- Demonstrated in vivo interaction between Aurora-A and VHL, identifying Ser72 on VHL as the phosphorylation site by Aurora-A.
Conclusions:
- Aurora-A expression is linked to tumor aggressiveness and VHL status in ccRCC.
- Aurora-A and VHL interact, suggesting a role in ccRCC pathogenesis.
- Phosphorylation of VHL by Aurora-A at Ser72 is a key molecular event in ccRCC.
