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| Status |
Public on Nov 05, 2025 |
| Title |
Genetic vulnerabilitis study in VHL mutant cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
VHL has been known as a tumour suppressor gene, also is an essential gene for some proteolysis-targeting chimera (PROTAC) degraders. Here by using CRISPR-cas9 genome wide screening we find that VHL mutation results in strong proliferation defect by HIF1A . VHL MUT shows malfunction of mitochondria which can be restored by HIF1A inhibition. VHL MUT bear specific genetic vulnerabilities which are druggable and mainly HIF1A dependent. In OE33 and MCF7, additional HIF1A inhibition on VHL MUT allows a complete ARV-771 drug resistance acquisition. Our study reports the consequence of VHL mutation and HIF1A dependent druggable genetic vulnerabilities in VHL mutant renal epithelial cells and possible PROTAC resistance acquisition mechanism in breast and oesophageal cancers, provides potential therapeutic targets and strategies for early precancerous and established cancerous cells.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for VHL WT HK2 clones (D-C8, D-C10, D-C35) and VHL KO HK2 clones (C8, C10, C35).
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| Contributor(s) |
Ge J, Vanharanta S |
| Citation missing |
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| |
| Submission date |
Sep 13, 2022 |
| Last update date |
Nov 05, 2025 |
| Contact name |
Jianfeng Ge |
| E-mail(s) |
jg872@cam.ac.uk
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| Phone |
07405378114
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| Organization name |
University of Cambridge
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| Street address |
37, ST THOMAS'S SQUARE
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| City |
Cambridge |
| State/province |
Cambridgeshire |
| ZIP/Postal code |
CB1 3TG |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA880165 |
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