USP1 Maintains the Survival of Liver Circulating Tumor Cells by Deubiquitinating and Stabilizing TBLR1

Yuancheng Li; Yuancheng Li; Yang Xu; Chao Gao; Chao Gao; Yunfan Sun; Kaiqian Zhou; Pengxiang Wang; Jianweng Cheng; Wei Guo; Cao Ya; Jia Fan; Jia Fan; Xinrong Yang

doi:10.3389/fonc.2020.554809

Frontiers in Oncology (Sep 2020)

USP1 Maintains the Survival of Liver Circulating Tumor Cells by Deubiquitinating and Stabilizing TBLR1

Yuancheng Li,
Yuancheng Li,
Yang Xu,
Chao Gao,
Chao Gao,
Yunfan Sun,
Kaiqian Zhou,
Pengxiang Wang,
Jianweng Cheng,
Wei Guo,
Cao Ya,
Jia Fan,
Jia Fan,
Xinrong Yang

Affiliations

Yuancheng Li: Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Yuancheng Li: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Yang Xu: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Chao Gao: Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Chao Gao: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Yunfan Sun: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Kaiqian Zhou: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Pengxiang Wang: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Jianweng Cheng: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Wei Guo: Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Cao Ya: Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
Jia Fan: Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Jia Fan: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China
Xinrong Yang: Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China

DOI: https://doi.org/10.3389/fonc.2020.554809
Journal volume & issue: Vol. 10

Abstract

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The prognosis of hepatocellular carcinoma (HCC) is closely associated with the occurrence of distant metastases, which is likely due to circulating tumor cells (CTCs). However, the low number of CTCs is the main obstacle limiting research of the mechanism of CTC metastasis. Here, We evaluated the role of ubiquitin-specific protease 1 (USP1) in promoting CTC survival during blood-borne metastases. We observed that USP1 was frequently upregulated in CTCs and correlated with metastasis and a reduced overall survival rate of patients. Additionally, genetic knockout of USP1 the survival rate of CTCs. Further analyses showed that USP1 mediates oncogenic activity by deubiquitinating and stabilizing transducin β-like 1 X-linked receptor 1 (TBLR1), which plays essential roles in regulating Wnt signaling. These results demonstrated that USP1 may act as an essential factor in promoting the survival of CTCs and suggest that inhibition of USP1 is a potential strategy for HCC treatment.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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