hPCL3s Promotes Hepatocellular Carcinoma Metastasis by Activating β-Catenin Signaling

Abstract

Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic β-catenin destruction complex, inhibited β-catenin degradation, and activated β-catenin/T-cell factor signaling. Downstream of the β-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the β-catenin/IL6 pathway. hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the β-catenin/IL6 signaling axis to promote metastasis. .

Krüppel‐like factor 2 inhibits hepatocarcinogenesis through negative regulation of the Hedgehog pathway

“…In liver cancer, P53 deletion and the Kras G12D activating mutation are very common. Based on this, we established a model of spontaneous HCC (Alb‐Cre; P53 fl/fl ; Kras G12D ) by crossing Alb‐Cre mice with mice expressing LSL‐Kras G12D and P53 fl/fl . Simply, the Cre enzyme expressed by the mice is regulated by the Alb gene promoter.…”

“…These genes were cloned into the p23/pLKO.1 vectors or for transient (using the Lipofectamine 2000 according to the manufacturer's instructions; Thermo Fisher Scientific, Waltham, MA, USA) or stable expression in 7404 or Huh‐7 cells. The lentivirus was used to produce the stable transformants.…”

PHD Finger Protein 19 Enhances the Resistance of Ovarian Cancer Cells to Compound Fuling Granule by Protecting Cell Growth, Invasion, Migration, and Stemness

“…Generally, recruitment of PRC2 to DNA regions of target genes to catalyze the methylation of lysine 27 on histone 3 (H3K27me3), are essential for controlling the developmental gene expression and maintaining cell specification (Kouznetsova et al, 2019). Aberrant expression of PHF19 has been implicated in regulating the pathogenesis and progression of a wide range of cancers, including melanoma (Ghislin et al, 2012), hepatocellular carcinoma (Xu et al, 2015;Cai et al, 2018), glioma (Lu et al, 2018), glioblastoma (Deng et al, 2018), multiple myeloma (Ren et al, 2019). In our previous publication, we have found that patients with higher expression of PHF19 are associated with shorter progressionfree survival (PFS) than that with lower PHF19 expression.…”

HSP90 interacts with HMGCR and promotes the progression of hepatocellular carcinoma

“…Membranes were blocked with 5% milk at room temperature for 1 h, and probed with primary and secondary antibodies. The immunoreactive protein bands were visualized using an Enhanced Chemiluminescence kit (Pierce; Thermo Fisher Scientific, Inc. Staining was assessed using the H-score method (21), according to the following equation: H-score=Σ(i x Pi). The staining intensity i) of the tumour cells was graded from 0-3, and Pi was the percentage of stained cells at each staining intensity.…”