![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
![[thumbnail of Supplementary Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information)
3MB |
| Item Type: | Article |
|---|---|
| Title: | Integrated multi-omics analysis of RB-loss identifies widespread cellular programming and synthetic weaknesses |
| Creators Name: | Rajasekaran, S., Siddiqui, J., Rakijas, J., Nicolay, B., Lin, C., Khan, E., Patel, R., Morris, R., Wyler, E., Boukhali, M., Balasubramanyam, J., Ranjith Kumar, R., Van Rechem, C., Vogel, C., Elchuri, S.V., Landthaler, M., Obermayer, B., Haas, W., Dyson, N. and Miles, W. |
| Abstract: | Inactivation of RB is one of the hallmarks of cancer, however gaps remain in our understanding of how RB-loss changes human cells. Here we show that pRB-depletion results in cellular reprogramming, we quantitatively measured how RB-depletion altered the transcriptional, proteomic and metabolic output of non-tumorigenic RPE1 human cells. These profiles identified widespread changes in metabolic and cell stress response factors previously linked to E2F function. In addition, we find a number of additional pathways that are sensitive to RB-depletion that are not E2F-regulated that may represent compensatory mechanisms to support the growth of RB-depleted cells. To determine whether these molecular changes are also present in RB1(−/−) tumors, we compared these results to Retinoblastoma and Small Cell Lung Cancer data, and identified widespread conservation of alterations found in RPE1 cells. To define which of these changes contribute to the growth of cells with de-regulated E2F activity, we assayed how inhibiting or depleting these proteins affected the growth of RB1(−/−) cells and of Drosophila E2f1-RNAi models in vivo. From this analysis, we identify key metabolic pathways that are essential for the growth of pRB-deleted human cells. |
| Keywords: | Retinal Neoplasms, Retinoblastoma, Retinoblastoma Binding Proteins, Tumor Cell Line, Ubiquitin-Protein Ligases, Animals, Mice |
| Source: | Communications Biology |
| ISSN: | 2399-3642 |
| Publisher: | Springer Nature |
| Volume: | 4 |
| Number: | 1 |
| Page Range: | 977 |
| Date: | 17 August 2021 |
| Additional Information: | Erratum in: Commun Biol 4(1): 1156. |
| Official Publication: | https://doi.org/10.1038/s42003-021-02495-2 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
