SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

Cancer Research
Liang-Zhi WenWei-Fen Xie

Abstract

Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1, also known as PTPN6) is a nonreceptor protein tyrosine phosphatase that acts as a negative regulator of inflammation. Emerging evidence indicates that SHP-1 plays a role in inhibiting the progression of hepatocellular carcinoma (HCC). However, the role of SHP-1 in hepatocarcinogenesis remains unknown. Here, we find that levels of SHP-1 are significantly downregulated in human HCC tissues compared with those in noncancerous tissues (P < 0.001) and inversely correlate with tumor diameters (r = -0.4130, P = 0.0002) and serum α-fetoprotein levels (P = 0.047). Reduced SHP-1 expression was associated with shorter overall survival of patients with HCC with HBV infection. Overexpression of SHP-1 suppressed proliferation, migration, invasion, and tumorigenicity of HCC cells, whereas knockdown of SHP-1 enhanced the malignant phenotype. Moreover, knockout of Ptpn6 in hepatocytes (Ptpn6 HKO ) enhanced hepatocarcinogenesis induced by diethylnitrosamine (DEN) as well as metastasis of primary liver cancer in mice. Furthermore, systemic delivery of SHP-1 by an adenovirus expression vector exerted a therapeutic effect in an orthotopic model of HCC in NOD/SCID mice and DEN-indu...Continue Reading

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Citations

Apr 22, 2020·Cancer Biotherapy & Radiopharmaceuticals·Ximing Gong, Zhenya Zhu
Jan 7, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhibin LiaoXiaoping Chen
May 27, 2020·Disease Markers·Chengquan ShenYonghua Wang
Jun 10, 2020·Cancer Cell International·Guoqing OuyangXiang Chen
Feb 6, 2021·Biological Chemistry·Stefano Piatto ClericiCarmen Veríssima Ferreira-Halder
Apr 24, 2021·Frontiers in Cell and Developmental Biology·Xiaohua HuangGanggang Shi
Jun 6, 2021·Cell Communication and Signaling : CCS·Alessia VaroneDaniela Corda
Jun 1, 2021·European Journal of Pharmacology·Ching-Kai ShenCheng-Fang Tsai
Jun 19, 2021·The Journal of Allergy and Clinical Immunology·Doumet Georges HelouOmid Akbari

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