Journal
CELL REPORTS
Volume 24, Issue 5, Pages 1093-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.06.106
Keywords
-
Categories
Funding
- Italian Association for Research on Cancer (AIRC) [IG14382, IG18706]
- Umberto Veronesi Foundation
- Medical Research Council (MRC)
- MRC [MC_UU_12022/6] Funding Source: UKRI
Ask authors/readers for more resources
Renal cell carcinomas (RCCs) are common cancers diagnosed in more than 350,000 people each year worldwide. Several pathways are de-regulated in RCCs, including mTORC1. However, how mTOR drives tumorigenesis in this context is unknown. The lack of faithful animal models has limited progress in understanding and targeting RCCs. Here, we generated a mouse model harboring the kidney-specific inactivation of Tsc1. These animals develop cysts that evolve into papillae, cystadenomas, and papillary carcinomas. Global profiling confirmed several metabolic derangements previously attributed to mTORC1. Notably, Tsc1 inactivation results in the accumulation of fumarate and in mTOR-dependent downregulation of the TCA cycle enzyme fumarate hydratase (FH). The re-expression of FH in cellular systems lacking Tsc1 partially rescued renal epithelial transformation. Importantly, the mTORC1-FH axis is likely conserved in human RCC specimens. We reveal a role of mTORC1 in renal tumorigenesis, which depends on the oncometabolite fumarate.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available