Nuclear-factor-kappaB (NF-kappaB) and radical oxygen species play contrary roles in transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in hepatocellular carcinoma (HCC) cells.
In present study, we have found that TGF-beta1 down-regulates PTEN mRNA and protein expression in a dose- and time-dependent manner in hepatocarcinoma cell line SMMC-7721.
Here we examined a human hepatocellular carcinoma cell line (Hep3B-TS) sensitive to TGF-beta signalling, and a derivative line (Hep3B-TR) rendered resistant to TGF-beta by stepwise exposure to TGF-beta(1).
These studies indicated that TGF-beta 1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells.
Furthermore, the number of LAP<sup>+</sup>CD4<sup>+</sup> T cells per high-magnification microscopic field (magnification, ×400) in the HCC tissues was 11.25±3.00, which was significantly higher than that in the peri-cancer tissues (5.75±1.00) and that in the HBV-infected hepatic tissues around benign lesions (2.61±0.83).
SIGNIFICANCE: These findings show that reduced number and function of CD160<sup>+</sup> NK cells in the tumor microenvironment contributes to immune escape of HCC; blocking TGFβ1 restores IFNγ production of CD160<sup>+</sup> NK cells.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/78/23/6581/F1.large.jpg.
In the current study, we report that GnT-V-mediated N-glycosylation of CD147/basigin, a tumor-associated glycoprotein that carries β1,6-N-acetylglucosamine (β1,6-GlcNAc) glycans, is upregulated during TGF-β1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC).
To further delineate whether tamoxifen may be of benefit in altering the course of HCC, we documented the effects of 4-hydroxytamoxifen and 17beta-estradiol on TGF-beta1 mRNA and protein levels and cell proliferation in a human HCC cell line.
Lung fibroblast-conditioned medium stimulated TGF-β1 production from LCCs, whereas LCC-conditioned medium decreased fibroblast survival and α-smooth muscle actin expression by fibroblasts.
Our study shows that Ln-5 and TGF-beta1 cooperatively induce EMT in HCC, suggesting the microenvironment as a potential target for new biological therapies.
In conclusion, our meta-analysis indicates that TGF-β1-509C/T (or +869T/C) polymorphism was not associated with risk of HCC, although a marginal association was found for Caucasians.
Here we report that H2O2 and HOCl, the reactive oxygen species produced by neutrophils, could cooperate with TGF-β1 to induce metastatic phenotype of non-metastatic hepatocellular carcinoma (HCC) cells.
In analysis of correlation with tumor stage, both protein and mRNA expression of TGFβ1, Smad1, Smad2 and Smad4 in patients with stage III HCC were significantly lower than those with stage IV HCC (P < 0.001), while the protein and mRNA expression of Smad3 in patients with IV stage HCC was significantly higher in comparison to those with stage IV HCC (P < 0.001).
TGF-β1-induced phosphorylation of Smad2 and Akt was enhanced in RIG-I-deficient HCC spheres, knockdown of AKT gene expression abolishing the augmentation of TGF-β1-induced Smad2 phosphorylation.
Immobilized Transforming Growth Factor-Beta 1 in a Stiffness-Tunable Artificial Extracellular Matrix Enhances Mechanotransduction in the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma.
Molecularly, oncogenicity of Tgfb1 in HCC was dependent on the switch of dominant activated signaling pathway from Smad to Erk in hepatocytes while concurrent activation of both Smad and Erk pathways in cholangiocytes was essential for Tgfb1-induced CCA.