| First Author | Wen LZ | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 16 | Pages | 4680-4691 |
| PubMed ID | 29776962 | Mgi Jnum | J:264292 |
| Mgi Id | MGI:6195945 | Doi | 10.1158/0008-5472.CAN-17-3896 |
| Citation | Wen LZ, et al. (2018) SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression. Cancer Res 78(16):4680-4691 |
| abstractText | 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 alpha-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-induced primary liver cancers in Ptpn6(HKO) mice. In addition, SHP-1 inhibited the activation of JAK/STAT, NF-kappaB, and AKT signaling pathways, but not the MAPK pathway in primary hepatocytes from DEN-treated mice and human HCC cells. Together, our data implicate SHP-1 as a tumor suppressor of hepatocarcinogenesis and HCC progression and propose it as a novel prognostic biomarker and therapeutic target of HCC.Significance: The nonreceptor protein tyrosine phosphatase SHP-1 acts as a tumor suppressor in hepatocellular carcinoma. Cancer Res; 78(16); 4680-91. (c)2018 AACR. |
