title: Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma.
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.
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Jin
authors.forename: Kaimei
authors.initials: K
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.forename: Junyao
authors.initials: J
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Chu
authors.forename: Dechen
authors.initials: D
authors.lastname: Lin
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Koeffler
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
mesh_terms: D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C490198:PTP4A1 protein, human; D017027:Protein Tyrosine Phosphatases