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

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

doi:10.3389/fonc.2020.554809

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

Front Oncol. 2020 Sep 25:10:554809. doi: 10.3389/fonc.2020.554809. eCollection 2020.

Authors

Yuancheng Li^{1

2}, Yang Xu², Chao Gao^{1

2}, Yunfan Sun², Kaiqian Zhou², Pengxiang Wang², Jianweng Cheng², Wei Guo³, Cao Ya⁴, Jia Fan^{1

2}, Xinrong Yang²

Affiliations

¹ Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
² Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China.
³ Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.

Abstract

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.

Keywords: USP1; Wnt pathway; circulating tumor cells; deubiquitination; hepatocellular carcinoma.