|
| Status |
Public on Jan 27, 2024 |
| Title |
Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Notably, LD accumulation is prevented, and tumor burden reduced in vivo upon concurrent inhibition of MYC signaling and glutamine metabolism. Furthermore, we identified the hypoxia inducible lipid droplet associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples, postulated HILPDA as a specific ccRCC biomarker. Together, these discoveries provide an attractive approach for development of new therapeutic interventions for the treatment of this type of renal cancer.
|
| |
|
| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for clear cell renal cell carcinoma cell line RCC4 with loss of VHL gene (RCC4 VHL-) and the same cell line wirh VHL reintroduction (RCC4 VHL+) These two cell lines were treated with either control (DMSO) or MYC inhibitor JQ1.
|
| Web link |
https://www.pnas.org/doi/10.1073/pnas.2310479121
|
| |
|
| Contributor(s) |
Sainero-Alcolado L, Garde-Lapido E, Snaebjörnsson MT, Schoch S, Stevens I, Ruiz-Pérez M, Dyrager C, Pelechano V, Axelson H, Schulze A, Arsenian-Henriksson M |
| Citation(s) |
38335255 |
| Submission date |
Jan 17, 2023 |
| Last update date |
Feb 10, 2024 |
| Contact name |
Irene Stevens |
| E-mail(s) |
irene.stevens@scilifelab.se
|
| Phone |
0046728774966
|
| Organization name |
Karolinska Institutet
|
| Department |
Department of Microbiology, Tumor and Cell Biology
|
| Lab |
Pelechano
|
| Street address |
Tomtebodavägen 23A (Gamma5)
|
| City |
Solna |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
| |
|
| Platforms (1) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA924799 |
Less...
More...