Related Experiment Video
Updated: Aug 29, 2025
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression
Tao Hou1,2,3, Weichao Dan1,2,3, Tianjie Liu1,2,3
1Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.
Abstract:
The mechanistic (formally "mammalian") target of rapamycin (mTOR) pathway serves as a crucial regulator of various biological processes such as cell growth and cancer progression. In bladder cancer, recent discoveries showing the cancer-promoting role of mTOR complex 1 have attracted wide attention. However, the regulation of mTOR signaling in bladder cancer is complicated and the underlying mechanism remains elusive. Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. In our study, we found that OTUD5 deubiquitinated a RING-type E3 ligase, RNF186, and stabilized its function. In addition, the stabilization of RNF186 further led to the degradation of sestrin2, which is an inhibitor of the mTOR signaling pathway. Together, we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.
Insights
Ovarian tumor domain-containing protein 5 (OTUD5) activates the mechanistic target of rapamycin (mTOR) pathway, promoting bladder cancer. This occurs via the OTUD5-RNF186-sestrin2-mTOR axis, offering potential diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The mechanistic target of rapamycin (mTOR) pathway is vital for cell growth and cancer, with mTOR complex 1 implicated in bladder cancer progression.
- Understanding mTOR regulation in bladder cancer is crucial, as current mechanisms remain largely unknown.
Purpose of the Study:
- To investigate the role of ovarian tumor domain-containing protein 5 (OTUD5) in bladder cancer.
- To elucidate the mechanism by which OTUD5 influences the mTOR signaling pathway in bladder cancer.
Main Methods:
- Investigated the deubiquitinating enzyme OTUD5's function in bladder cancer.
- Analyzed the interaction between OTUD5, RNF186, sestrin2, and the mTOR pathway.
- Utilized molecular biology techniques to determine the regulatory axis.
Main Results:
- OTUD5 activates the mTOR signaling pathway and promotes bladder cancer progression.
- OTUD5 deubiquitinates and stabilizes the E3 ligase RNF186.
- RNF186 promotes sestrin2 degradation, an inhibitor of the mTOR pathway.
Conclusions:
- OTUD5 exhibits oncogenic potential in bladder cancer by activating mTOR signaling.
- The study identifies a novel OTUD5-RNF186-sestrin2-mTOR signaling axis in bladder cancer pathogenesis.
- This axis presents potential targets for future bladder cancer diagnosis and treatment.
More Related Videos
09:40Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
10:25Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology
Published on: November 22, 2024
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
02:23Abnormal Proliferation