Protein Tyrosine Phosphatase 4a3 (PTP4a3) Regulates Cell Proliferation And Metastasis In Hepatocellular Carcinoma

Protein Tyrosine Phosphatase 4a3(PTP4a3)is a kind of phosphatase,which belongs to the dual specificity phosphatases(DUSPs)family.DUSPs act upon vastly diverse substrates and can dephosphorylate tyrosine,serine or threonine residues.Several studies suggest that PTP4a3 may be involved in the proliferation and metastasis of colorectal cancer,gastric cancer,breast cancer,lung cancer,multiple myeloma and other malignant tumors.However,little is known about the functional roles of PTP4a3 and its underlying mechanism in hepatocellular carcinoma(HCC)The analysis results of the cancer genome atlas(TCGA)database showed that PTP4a3 expression was higher in HCC tumor tissues than in non-tumor tissues(P<0.0001).Kaplan-Meier survival curve analysis also suggested the patients with high PTP4a3 expression may experience poorer survival situation(P=0.036).Q-PCR results of 81 pairs of HCC cDNA samples showed that patients highly expressing PTP4a3 took up about 79.0% of total patients.The content of alpha fetoprotein(AFP)was higher in HCC patients with high PTP4a3 expression,and high AFP is also an important index of HCC clinical examination.As for in vitro cell experiments,PTP4a3 were overexpressed in HCC cell lines SNU449 and CRL-8024.As a result,the ability of proliferation and metastasis were improved in PTP4a3 overexpressing cells.By contrast,knock down of PTP4a3 in CRL-8024 would inhibit cell proliferation.In addition,liver-specific PTP4a3 knock-out mice were administrated with specific carcinogens to construct induced HCC tumor model,which helped us explore the effects of PTP4a3 on tumor progress in vivo.Other animal models,such as ectopic xenograft and orthatopic xenograft in immunodeficient mice,will also be adopted to demonstrate the eff ects of PTP4a3 on HCC development and metastasis.The role of PTP4a3 in the development of HCC will be demonstrated from in vitro and in vivo respectively.