Downregulation of Notch1 inhibits the invasion of human hepatocellular carcinoma HepG2 and MHCC97H cells through the regulation of PTEN and FAK

Abstract

Tumor invasion and metastasis are the main causes of mortality in patients with hepatocellular carcinoma (HCC). Thus, the effective inhibition of these tumorigenic processes is critical in order for HCC therapy to be effective. Previous studies have demonstrated that Notch1 is associated with metastasis in several human malignancies. However, the exact molecular mechanisms underlying the Notch1-mediated induction of the invasion of HCC cells remain poorly understood. In the present study, we demonstrate that, compared to the normal liver cell line, L02, Notch1 is highly expressed in the human HCC cell lines, HepG2 and MHCC97H. Using small interfering RNA (siRNA), we knocked down the expression of Notch1 in the cell lines. Notch1 expression in the HCC cell lines was also measured following transfection with siRNA using RT-PCR and western blot analysis. In addition, a migration and invasion assay was performed to determine the effects of Notch1 knockdown on cell migration and invasion. Our results demonstrated that the downregulation of Notch1 by small interfering RNA (siRNA) significantly inhibited the migration and invasion of both HCC cell lines. Additionally, we demonstrated that the knockdown of Notch1 in both HCC cell lines increased both the total expression of phosphatase and tensin homolog (PTEN) and its phosphorylated form. By contrast, focal adhesion kinase (FAK) and phospho-FAK expression was decreased following Notch1 depletion. Taken together, our data suggest that targeting Notch1 may be a useful therapeutic approach to inhibiting the metastasis of HCC cells.

Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway

“…PTEN is often downregulated in cancers and functions to control important cellular processes, including survival, proliferation, migration, and invasion, which is vital for tumor cells to disseminate to adjacent or distant tissues, and finally causes distant metastasis-related recurrence (Davies et al, 2015;Jaraiz-Rodriguez et al, 2017). More importantly, PTEN gene transcription was regulated by Notch1 signaling pathway activation in various cancers (Hu et al, 2014;Kim et al, 2016;Zhou et al, 2013). In this study, we also found that increased phosphorylation of AKT in breast cancer cells through Plac1-induced PTEN downregulation can be reversed by Furin knockdown, suggesting that Plac1 controls conversion of cancer cells into an invasive and metastatic state by regulating the Furin/ NICD/PTEN/AKT axis.…”

HES5 promotes cell proliferation and invasion through activation of STAT3 and predicts poor survival in hepatocellular carcinoma

“…We validated that HES5 interacted with STAT3 in the HepG2 cells, and knockdown HES5 could reduce the relationship between the HES5 and STAT3 and inhibit the activity of STAT3. It has study shown that Notch is highly expressed in the human HCC cell lines as compared with the normal liver cell line (Hu et al, 2014). And study also shown that Notch signaling was found to be aberrantly up-regulated in HCC tissues compared with normal liver tissues (Sun et al, 2015).…”

Expression of B-cell translocation gene 2 is associated with favorable prognosis in hepatocellular carcinoma patients and sensitizes irradiation-induced hepatocellular carcinoma cell apoptosis in vitro and in nude mice

“…Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality, and ranks sixth among the most common cancers in the world (1)(2)(3). HCC is usually diagnosed at the advanced stage due to the lack of early detection methods such as serum biomarkers, or clinical symptoms and signs; this means that surgical cure is impossible.…”