Prostate-derived ETS factor improves prognosis and represses proliferation and invasion in hepatocellular carcinoma

Abstract

Prostate-derived E-twenty-six (ETS) factor (PDEF), an epithelium-specific ETS transcription factor, regulates carcinogenesis and tumor progression. The prognostic importance and biologic functions in hepatocellular carcinoma (HCC) have not been established. We investigated PDEF expression in 400 HCC patients using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analysis. PDEF expression was significantly lower in tumors than in peritumoral tissues. Lower PDEF levels were associated with poorer prognosis in patients. PDEF was an independent predictor of overall survival in multivariate analysis. PDEF expression was suppressed in highly metastatic HCC cell lines, and shRNA-mediated down-regulation of PDEF in low-metastatic HCC cell lines (with high PDEF) significantly increased cellular proliferative and invasive capacity in vitro and in vivo. RNA sequencing analysis indicated that PDEF may mediate transcription of several genes involved in apoptosis and the cell cycle. PDEF modulated epithelial-mesenchymal transition by up-regulating E-cadherin expression and down-regulating Slug and Vimentin expression, thereby lowering migration and invasion abilities of HCC cells. In conclusion, PDEF is associated with proliferation and invasiveness of HCC cells. It may serve as an independent predictor of prognosis in patients with HCC.

The miR-561-5p/CX3CL1 Signaling Axis Regulates Pulmonary Metastasis in Hepatocellular Carcinoma Involving CX3CR1+ Natural Killer Cells Infiltration

“…These patients were post-surgically monitored until July 7, 2015, with a median follow-up of 54 months (range: 1-66 months). The follow-up procedures were performed as described in our previous reports 17. The patients did not exhibit signs of distant metastasis.…”

ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer

“…SPDEF mRNA and protein expression is reduced in HCC, particularly in poorly differentiated tumours, and is associated with worse patient outcome [ 98 ]. Knockdown of SPDEF in HCC cell lines increased cell proliferation, survival and invasion in vitro and tumour growth and metastasis in vivo.…”

“…The increased invasion and metastasis are likely due to increased expression of the EMT driver, SLUG. Comparatively, overexpression of SPDEF in HCC cell lines decreased proliferation and increased apoptosis [ 98 ].…”

AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer

“…Studies on BC have shown that PDEF promotes the luminal differentiation of basal mammary epithelial cells and contributes to endocrine resistance in ER-positive BC [ 13 ]. In contrast, other studies have shown that PDEF levels decrease in highly malignant, ER-negative and basal-like BC cells and that re-expression of PDEF in these cells reduces their migration and invasion, suggesting that PDEF functions as a tumour suppressor [ 33 , 34 ]. It is difficult to assess the relevance of ectopic PDEF expression in tumour cell lineages.…”

“…Studies assessing PDEF function in different cancers suggest its important role in tumorigenesis [ 32 , 33 ]. Studies on BC have shown that PDEF promotes the luminal differentiation of basal mammary epithelial cells and contributes to endocrine resistance in ER-positive BC [ 13 ].…”