Aberrant activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is related to clinicopathological features of HCC.
Tumor cells from these mice demonstrated high activity of the AKT/ mammalian target of rapamycin (mTOR) and Ras/ Mitogen-activated protein kinase (MAPK) signaling cascades, two pathways frequently co-induced in human HCC.
Through protein and histological analyzes we observed activation of these pathways in human HCC, suggesting that targeting both mTOR and Src may be a novel approach for the treatment of HCC.
Although the review focuses on the mTOR pathway involved in HCC, more comprehensive discussions (eg, developing a rational design for future trials targeting the mTOR pathway) are also applicable to other tumors.
Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKα/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis.
PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; <i>P</i> < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; <i>P</i> < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death.
SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).
Antitumor effect of sorafenib and mammalian target of rapamycin inhibitor in liver transplantation recipients with hepatocellular carcinoma recurrence.
Immunohistochemical analysis showed that mTOR was characteristically phosphorylated in liver tumors of TSOD mice and HCCs from metabolic syndrome cases in humans.
Significance and mechanism of androgen receptor overexpression and androgen receptor/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma.
Indeed, BC suppresses autophagy induced by an mTORC1 inhibitor and synergizes cell death caused by mTORC1 inhibition in TIC and Huh7 spheroid formation and in the patient-derived xenograft model of HCC.
Co-Localization of Insulin-Like Growth Factor Binding Protein-1, Casein Kinase-2β, and Mechanistic Target of Rapamycin in Human Hepatocellular Carcinoma Cells as Demonstrated by Dual Immunofluorescence and in Situ Proximity Ligation Assay.
Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib.
Choline Kinase α Mediates Interactions Between the Epidermal Growth Factor Receptor and Mechanistic Target of Rapamycin Complex 2 in Hepatocellular Carcinoma Cells to Promote Drug Resistance and Xenograft Tumor Progression.
Anthracimycin is a novel mTOR inhibitor capable of suppressing the proliferation of CSCs and non-CSCs equally well in HCC, and it is suggested that anthracimycin could be effective in the eradication of HCC associated with mTOR-signaling activation.
We have shown previously that rapamycin, the canonical inhibitor of the mechanistic target of rapamycin (mTOR) complex 1, markedly inhibits the growth of focal lesions in the resistant hepatocyte (Solt-Farber) model of hepatocellular carcinoma (HCC) in the rat.
These results suggest that mTOR-STAT3-HK2 pathway is involved in the glycolysis of HCC cells and STAT3 may regulate HCC glycolysis through HK2 pathway, providing potential multiple therapeutic targets through intervention of glycolysis for the treatment of HCC.
Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC).