Table 1.
Protein tyrosine phosphatases (PTPs) discussed in this review with their potential role in hepatocellular carcinoma.
| PTPs | Observations | TSG or Onco | Ref. | |
|---|---|---|---|---|
| Receptor PTPs | PTPRD | PTPRD expression was downregulated or loss; High expression of PTPRD has a long-term survival rate and less chance of recurrent liver cancer. | TSG | [7,8] |
| PTPRF | PTPRF was frequent downregulated in most of HCC patients, and upregulation of PTPRF associated with better prognosis. PTPRF suppressed cell proliferation, colony formation in vitro and inhibited tumor growth in vivo. | TSG | [9] | |
| PTPRH | PTPRH expression in moderately differentiated HCCs and in all poorly differentiated HCCs was greatly reduced or loss. Overexpression of PTPRH reduce both migratory activity and growth rate of cells | TSG | [10] | |
| PTPRO | PTPRO expression was significantly reduced in human HCC specimens. Overexpression of PTPRO promoted apoptosis i and nhibited proliferation in vitro, and tumor size and number were increased in PTPRO knockout mice. | TSG | [11] | |
| PTPRS | Downregulation of PTPRS was observed in HCC cell lines and samples, and significantly associated with decreased overall survival and high risk of recurrence. PTPRS silencing promoted cell proliferation, migration and invasion both in vitro and in vivo. | TSG | [12] | |
| PTPRT | Increased expression of PTPRT in HepG2-xΔ127 cells treated decreased the tumor weight and volume in vivo | TSG | [13] | |
| non-receptor PTPs | PTP1B | PTP1B prime protein degradation of PITX1 to reduce p120RasGAP transcription. | Onco | [14] |
| Patients with low PTP1B expression had either shorter disease-free survival or worse overall survival. PTP1B could reduce phosphorylation of MET receptor to block vascular invasion and metastasis. | TSG | [15,16] | ||
| PTPN9 | PTPN9 expression was significantly reduced in tumor tissues, and low expression of PTPN9 predicted poor survival. PTPN9 silencing reduced apoptosis and promoted proliferation in HepG2 cells. | TSG | [17] | |
| PTPN12 | PTPN12 expression is frequently decreased or loss in HCC tissues. down-regulation of PTPN12 also significantly increased the migration of HCC cell lines. | TSG | [18] | |
| PTPN13 | PTPN13 expression was often downregulated or loss in HCC tissues and HCC cell lines, and positively correlated with overall survival but negatively correlated with the recurrence rate. Overexpression of PTPN13 inhibit EMT in HCC progression. | TSG | [19,20] | |
| SHP-1 | SHP-1 expression has a negative correlation with p-STAT3 Tyr705 in HCC, and SHP-1 overexpression abolished TGF-β1-induced p-STAT3 Tyr705. | TSG | [21] | |
| SHP-2 | SHP2 knockout mice result in development of tumors and enhance diethylenenitrite (DEN)-induced HCC development. | Onco | [22] | |
| low Shp2 expression was significantly associated with short overall survival time. SHP2 could promote HCC cell growth and metastasis by coordinately activating the Ras/Raf/Erk pathway and the PI3-K/Akt/mTOR cascade. | TSG | [23] | ||
| DUSPs | PRL1 | High PRL-1 expression was associated with more aggressive phenotype and poorer prognosis in HCC patients. Overpression of PRL-1 markedly enhanced migration and invasion of HCC cells. | Onco | [24,25] |
| PRL-3 | PRL-3 expression (both mRNA and protein) was significantly associated with poor differentiation and prognosis, and positive correlation with matrix metalloproteinase MMP1, MMP9, MMP10 and MMP12. | Onco | [26] | |
| DUSP1 | High DUSP1 expression was associated with better prognosis. In rat models, low DUSP1 expression was more susceptible to develop HCC. | TSG | [27,28] | |
* TSG: Tumor suppressor gene; Onco: Oncogene; PTPRD: protein tyrosine phosphatase receptor delta; PTPRF: protein tyrosine phosphatase receptor type F; PTPRH: protein tyrosine phosphatase receptor type H; PTPRO: protein tyrosine phosphatase receptor type O; PTPRS: protein tyrosine phosphatase receptor S; PTPRT: protein tyrosine phosphatase receptor T; PTP1B: protein tyrosine phosphatase 1B; PTPN: protein tyrosine phosphatase, non-receptor; SHP: Src homology 2-containing phosphotyrosine phosphatase; PRL: phosphatase of regenerating liver; DUSPs: dual specificity phosphatases; HCC: hepatocellular carcinoma; MET: mesenchymal-epithelial transition factor; STAT3: signal transducer and activator of transcription 3; Tyr705: tyrosine 705; TGF: transforming growth factor; Ras/Raf/Erk:rat sarcoma/ rapidly accelerating fibrosarcoma/ extracellular signal-regulated kinase; PI3-K/Akt/mTOR: phosphotidylinsitol-3-OH kinase/ alpha serine/threonine-protein kinase/mechanistic target of rapamycin.