USP20 mediates malignant phenotypic changes in bladder cancer through direct interactions with YAP1
Wensun Chen1, Siqi Wu1, Yifan Chen1
1Department of Urology, Huashan Hospital Fudan University Shanghai, PR China.
Neoplasia (New York, N.Y.)
|December 14, 2024
Summary
USP20 deubiquitinase stabilizes YAP1 protein, promoting bladder cancer progression. This finding reveals USP20 as a key regulator of the Hippo-YAP1 pathway in bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The Hippo-YAP1 pathway is crucial in cancer, with its inhibition driving bladder cancer (BC) progression.
- The Hippo pathway's activity is modulated by phosphorylation and ubiquitination of its components.
- Deubiquitinases (DUBs) and E3 ligases co-regulate Hippo pathway protein ubiquitination.
Purpose of the Study:
- To identify novel deubiquitinases regulating the Hippo-YAP1 pathway in bladder cancer.
- To investigate the role of USP20 in the context of bladder cancer and the Hippo-YAP1 pathway.
Main Methods:
- siRNA screening to identify potential DUBs.
- Deubiquitinase overexpression assays.
- Western blotting to assess protein levels and ubiquitination.
- Tissue microarray analysis to evaluate USP20 expression in tumor tissues.
- Co-immunoprecipitation to confirm protein interactions.
Main Results:
- USP20 was identified as a deubiquitinase involved in the Hippo-YAP1 pathway.
- USP20 directly regulates YAP1 expression and its downstream targets (CTGF, CYR61).
- USP20 expression is elevated in bladder tumor tissues and correlates with YAP1 expression.
- USP20 interacts with YAP1 and enhances its stability by inhibiting K48-linked poly-ubiquitination.
Conclusions:
- USP20 functions as a deubiquitinase that stabilizes YAP1 protein.
- USP20 plays a significant role in regulating the Hippo-YAP1 pathway in bladder cancer.
- USP20 represents a potential therapeutic target for bladder cancer treatment.
More Related Videos
09:55All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
2.9K
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
6.7K
Related Concept Videos
02:23Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
01:12Loss of Tumor Suppressor Gene Functions
4.7K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.7K
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
01:20The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K