Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma

Abstract

Tissue factor (TF) is a transmembrane glycoprotein to initiate blood coagulation and frequently overexpressed in a variety of tumors. Our previous study has showed that the expression of TF is upregulated and correlated with prognosis in hepatocellular carcinoma (HCC). However, the role and molecular mechanism of TF in the growth of HCC are still unclear. In vitro and in vivo functional experiments were performed to determine the effect of TF on the growth of HCC cells. A panel of biochemical assays was used to elucidate the underlying mechanisms. TF could promote the growth of HCC in vitro and in vivo by activating both ERK and AKT signaling pathways. TF induced EGFR upregualtion, and inhibition of EGFR suppressed TF-mediated HCC growth. In addition, TF protein expression was correlated with EGFR in HCC tissues. TF promotes HCC growth by upregulation of EGFR, and TF as well as EGFR may be potential therapeutic targets of HCC.

Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation

“…The activation of EGFR in cancer cells is known to induce the activation of extracellular-regulated kinase (ERK) or Akt (protein kinase B; PKB) signaling pathways ( 67 , 68 ). Thus, we investigated the mRNA expression levels of ERK1/2 (also known as MAPK3/1) and AKT1 in porcine COCs after IVM.…”

A FITM1-Related Methylation Signature Predicts the Prognosis of Patients With Non-Viral Hepatocellular Carcinoma

“…Given that disorder lipid metabolism is closely associated with non-alcoholic fatty liver disease (NAFLD) and has been growingly considered a hallmark of cancer cells (Cingolani and Czaja, 2016;Tian et al, 2019), It is reasonable that MDGs exerted great impact on non-viral HCC through regulation of lipid metabolism and homeostasis. In addition, KEGG analysis suggested that EGFR and P53 pathways were also significantly enriched, which were involved in the pathogenesis and tumorigenesis of HCC (Xie et al, 2018;Huang et al, 2019).…”

Survivin Promotes Piperlongumine Resistance in Ovarian Cancer

“…Then, the viral supernatant was, respectively, collected 24, 48, 72, 96 h following transfection, filtered through a 0.20 μm filter, and concentrated. Using the polybrene (Solarbio, H8761), A2780, OVCAR-3 cells were transfected with pCDH-Neo-Venus-survivin or pCDH-Neo-Venus/DEST, followed by incubation with 48 h for the subsequent trials (17, 18).…”