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Updated: Aug 13, 2025
05:21
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
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USP7 inactivation suppresses APC-mutant intestinal hyperproliferation and tumor development
Laura Novellasdemunt1, Anna Kucharska1, Anna Baulies1
1Stem Cell and Cancer Biology Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Stem Cell Reports
|January 20, 2023
Summary
Targeting USP7 in colorectal cancer (CRC) shows promise. Inhibiting USP7 suppresses tumor growth in APC-mutated models, suggesting a potential therapy for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Adenomatous polyposis coli (APC) mutations drive colorectal cancer (CRC) via WNT pathway activation.
- Targeting WNT signaling is difficult due to on-target toxicity.
- USP7 was previously identified as a tumor-specific WNT activator in APC-truncated cells.
Purpose of the Study:
- To investigate the role of USP7 in intestinal tumorigenesis in vivo.
- To evaluate USP7 inhibition as a potential therapeutic strategy for APC-mutated CRC.
Main Methods:
- Genetic deletion of Usp7 in Apc-truncated mouse models.
- Pharmacological inhibition of USP7 in patient-derived cancer organoids and xenografts.
- Assessment of crypt hyperproliferation, tumor development, survival, and induction of colitis/enteritis.
Main Results:
- Usp7 deletion in Apc-truncated mice inhibited intestinal tumor development and prolonged survival.
- Genetic deletion of Usp7 induced colitis and enteritis, while pharmacological inhibition did not.
- USP7 inhibitors suppressed the growth of patient-derived APC-truncated CRC organoids and xenografts.
Conclusions:
- USP7 plays a critical role in gut tumorigenesis driven by APC mutations.
- USP7 inhibition demonstrates therapeutic potential for sporadic and germline APC-mutated CRC.
- USP7 inhibition offers a potentially safe and effective tumor-specific therapy for CRC.
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