Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma - 22/03/24

Doi : 10.1016/j.biopha.2024.116366

Renshun Dong ^a,^b,^c,^{^{1
These authors contributed equally to this work.}}, Tianci Wang ^a,^b,^c,^{^{1
These authors contributed equally to this work.}}, Wei Dong ^a,^b,^c,^d,^{^{1
These authors contributed equally to this work.}}, He Zhu ^a,^b,^c,^d, Qiumeng Liu ^a,^b,^c,^d, Huifang Liang ^a,^b,^c,^d, Xiaoping Chen ^a,^b,^c,^d,^⁎ , Bixiang Zhang ^a,^b,^c,^d,^⁎ , Xuewu Zhang ^a,^b,^c,^d,^⁎
^a Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
^b Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei 430030, China
^c Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, Hubei 430030, China
^d Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei 430030, China

^⁎Correspondence to: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan430030China

Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis, and the efficacy of current therapeutic strategies is extremely limited in advanced diseases. Our previous study reported that protein tyrosine phosphatase receptor epsilon (PTPRE) is a promoting factor in HCC progression. In this study, our objective was to evaluate the treatment effect of PTPRE inhibitors in different HCC preclinical models. Our results indicated that the PTPRE inhibitory compound 63 (Cpd-63) inhibited tumor cell proliferation, migration, and HCC organoid growth. Mechanism research revealed that Cpd-63 could inhibit the expression of MYC and MYC targets by inhibiting the activation of SRC. Additionally, we found that Cpd-63 could improve the response of sorafenib in HCC cells. In conclusion, we demonstrated that the PTPRE inhibitors represented a potential therapeutic agent for HCC management.

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Highlights

•	Targeting PTPRE selectively by small molecule is novel strategy for HCC therapy.
•	The PTPRE inhibitor Cpd-63 suppresses HCC progression in preclinical models.
•	Cpd-63 suppresses the expression of MYC by inhibiting the activation of SRC.
•	PTPRE inhibitors improve the response of sorafenib in HCC cells.

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Abbreviations : Cpd-52, Cpd-63, HCC, PDO, PLC, PTKs, PTPs, PTPRE

Keywords : PTPRE inhibitor, Hepatocellular carcinoma, Sorafenib, Organoid

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Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma - 22/03/24

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