Int J Biol Sci 2022; 18(8):3122-3136. doi:10.7150/ijbs.65428 This issue Cite

Research Paper

USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ

Putao Yuan1,2,3*, Zhenhua Feng1,2*, Hai Huang1,2,4*, Gangliang Wang1,2*, Zhijun Chen1,2,3, Guang Xu1,2, Ziang Xie1,2, Zhiwei Jie1,2, Xiangde Zhao1,2, Qingliang Ma1,2, Shiyu Wang1,2, Yang Shen1,2, Yizhen Huang1,2, Ying Han1,2, Huali Ye1,2, Jiying Wang1,2, Peihua Shi1,2,3✉, Xuewu Sun1,2,3✉

1. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine.
2. Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province.
3. Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
4. 903RD Hospital of Pla, Hangzhou, China.
*These authors contributed equally to this work.

Citation:
Yuan P, Feng Z, Huang H, Wang G, Chen Z, Xu G, Xie Z, Jie Z, Zhao X, Ma Q, Wang S, Shen Y, Huang Y, Han Y, Ye H, Wang J, Shi P, Sun X. USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. Int J Biol Sci 2022; 18(8):3122-3136. doi:10.7150/ijbs.65428. https://www.ijbs.com/v18p3122.htm
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Abstract

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Mutations and altered expression of deubiquitinating enzymes (DUBs) profoundly influence tumor progression. Ubiquitin-specific protease 1 (USP1) is a well-characterized human DUB reportedly overexpressed in and associated with maintaining the mesenchymal stem cell status of osteosarcoma (OS); however, the potential mechanisms of USP1 in OS remain poorly understood. In this study, we identified that USP1 directly interacts with Transcriptional Co-Activator With PDZ-Binding Motif (TAZ) in OS cell lines, and with mechanistic analysis indicating that the anti-OS effects of USP1 inhibition could be partially attributed to TAZ instability, with its reduced nuclear accumulation responsible for a subsequent decrease in the expression of downstream genes associated with the Hippo signaling pathway. Moreover, pharmacological inhibition USP1 by ML323 presented the similar effects on Hippo signaling pathway and suppressed OS growth and metastasis both in vitro and in vivo. Taken together, our results revealed a novel molecular mechanism underlying the function of USP1 in OS and a potential role of ML323 as a therapeutic strategy for the clinical treatment of OS.

Keywords: Osteosarcoma, USP1, TAZ, Hippo, Ubiquitin, ML323


Citation styles

APA
Yuan, P., Feng, Z., Huang, H., Wang, G., Chen, Z., Xu, G., Xie, Z., Jie, Z., Zhao, X., Ma, Q., Wang, S., Shen, Y., Huang, Y., Han, Y., Ye, H., Wang, J., Shi, P., Sun, X. (2022). USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. International Journal of Biological Sciences, 18(8), 3122-3136. https://doi.org/10.7150/ijbs.65428.

ACS
Yuan, P.; Feng, Z.; Huang, H.; Wang, G.; Chen, Z.; Xu, G.; Xie, Z.; Jie, Z.; Zhao, X.; Ma, Q.; Wang, S.; Shen, Y.; Huang, Y.; Han, Y.; Ye, H.; Wang, J.; Shi, P.; Sun, X. USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. Int. J. Biol. Sci. 2022, 18 (8), 3122-3136. DOI: 10.7150/ijbs.65428.

NLM
Yuan P, Feng Z, Huang H, Wang G, Chen Z, Xu G, Xie Z, Jie Z, Zhao X, Ma Q, Wang S, Shen Y, Huang Y, Han Y, Ye H, Wang J, Shi P, Sun X. USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. Int J Biol Sci 2022; 18(8):3122-3136. doi:10.7150/ijbs.65428. https://www.ijbs.com/v18p3122.htm

CSE
Yuan P, Feng Z, Huang H, Wang G, Chen Z, Xu G, Xie Z, Jie Z, Zhao X, Ma Q, Wang S, Shen Y, Huang Y, Han Y, Ye H, Wang J, Shi P, Sun X. 2022. USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. Int J Biol Sci. 18(8):3122-3136.

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