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- W3100809336 abstract "Abstract Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient 5-year survival rate is less than 5%. The ubiquitin specific protease 28 (USP28) has been implicated in tumorigenesis through its stabilization of the oncoprotein c-MYC. Here, we show that genetic inactivation of Usp28 induced regression of established murine LSCC lung tumors. We developed a small molecule that inhibits USP28 activity in the low nanomole range. While displaying cross-reactivity against the closest homologue USP25, this inhibitor showed a high degree of selectivity over other deubiquitinases. USP28 inhibitor treatment resulted in a dramatic decrease in c-Myc proteins levels and consequently induced substantial regression of autochthonous murine LSCC tumors and human LSCC xenografts, thereby phenocopying the effect observed by genetic deletion. Thus, USP28 may represent a promising therapeutic target for the treatment of squamous cell lung carcinoma." @default.
- W3100809336 created "2020-11-23" @default.
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- W3100809336 date "2020-11-17" @default.
- W3100809336 modified "2023-09-26" @default.
- W3100809336 title "USP28 deletion and small molecule inhibition destabilises c-Myc and elicits regression of squamous cell lung carcinoma" @default.
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- W3100809336 doi "https://doi.org/10.1101/2020.11.17.377705" @default.
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