Protein phosphatase 5 promotes hepatocarcinogenesis through interaction with AMP-activated protein kinase

Biochemical Pharmacology
Yao-Li ChenKuen-Feng Chen

Abstract

The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases. However, the role of PP5 in hepatocellular carcinoma (HCC) and whether PP5 may be a viable therapeutic target for HCC treatment are unknown. Here, by analyzing HCC clinical samples obtained from 215 patients, we found that overexpression of PP5 is tumor specific and associated with worse clinical outcomes. We further characterized the oncogenic properties of PP5 in HCC cells. Importantly, both silencing of PP5 with lentiviral-mediated short hairpin RNA (shRNA) and chemical inhibition of PP5 phosphatase activity using the natural compound cantharidin/norcantharidin markedly suppressed the growth of HCC cells and tumors in vitro and in vivo. Moreover, we identified AMP-activated protein kinase (AMPK) as a novel downstrea...Continue Reading

Citations

Apr 28, 2018·Journal of Hematology & Oncology·Ting LiJin-Jian Lu
Apr 3, 2020·Cell Stress & Chaperones·Rebecca A SagerMehdi Mollapour
May 9, 2021·Cellular Signalling·Joachim NeumannUlrich Gergs
Jun 23, 2021·Journal of Medicinal Chemistry·Qiuyue ZhangLei Wang

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