Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma.

Shaowen Jin,Kaimei Wang,Jie Wang,Dechen Lin,Zhonghua Chu,Kang Xu,Dong Yin,Jian Sun,Junyao Xu,Phillip H Koeffler

doi:10.18632/oncotarget.1986

Shaowen Jin, Kaimei Wang + Show 8 more

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https://doi.org/10.18632/oncotarget.1986

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Abstract

Our SNP-Chip data demonstrated 7/60 (12%) hepatocellular carcinoma (HCC) patients had PRL-1 copy number amplification. However, its biological functions and signaling pathways in HCC are deficient. Here, we investigated its oncogenic function and prognostic significance in HCC. PRL-1 protein levels were examined in 167 HCC samples by immunohistochemisty (IHC). The relationship of PRL-1 expression and clinicopathological features was assessed by correlation, Kaplan-Meier and Cox regression analyses. The oncogenic function of PRL-1 in HCC cells and its underlying mechanism were investigated by ectopic overexpression and knockdown model. PRL-1 levels in primary HCC and metastatic intravascular cancer thrombus were also determined by IHC. PRL-1 levels were frequently elevated in HCC tissues (81%), and elevated expression of PRL-1 was significantly associated with more aggressive phenotype and poorer prognosis in HCC patients (p<0.05). Ectopic overexpression of PRL-1 markedly enhanced HCC cells migration and invasion. Furthermore, the oncogenic functions of PRL-1 were mediated by PI3K/AKT/GSK3β signaling pathway through inhibiting E-cadherin expression. Finally, PRL-1 protein levels in metastatic cancer thrombus were higher than that in primary HCC tissues (p<0.05). These data highlight the oncogenic function of PRL-1 in HCC invasion and metastasis implicating PRL-1 as a potential prognostic marker as well as therapeutic target in HCC.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality [1,2]
Reversible tyrosine phosphorylation is critical for regulating the signaling pathways involved in tumor cell adhesion, invasion, and metastasis, It is governed by the balance between protein tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) [4]
These results suggested an oncogenic role for phosphatase of regenerating liver (PRL)-1 in cancer progression and metastasis

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality [1,2]. The phosphatase of regenerating liver (PRL) subgroup of PTPs, a unique class of prenylated phosphatases, had received much attention since PRL-3 was found to be the only gene consistently overexpressed in all 18 metastatic colorectal cancers [5]. A similar experiment [6] found that both the number and volume of hepatic metastatic foci decreased significantly in the mice injected with PRL-1-small interfering RNAtreated DLD-1 cells as compared to control cells. These results suggested an oncogenic role for PRL-1 in cancer progression and metastasis

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