Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma.

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. [Display omitted] • 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. [ABSTRACT FROM AUTHOR]