Therefore, how PTEN lipid phosphatase inactivation contributes to the occurrence and development of gastric cancer and the potential role of the Hippo and PI3K/Akt pathways in PTEN lipid phosphatase inactivation mediated gastric tumorigenesis remain to be explored.
Our study aimed to perform a molecular characterization of HER2-positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2-positive AGC treated with trastuzumab.
Through in vitro experiments, we proved that m6A suppression (represented by METTL14 knockdown) promoted GC cell proliferation and invasiveness through activating Wnt and PI3K-Akt signaling, while m6A elevation (represented by FTO knockdown) reversed these phenotypical and molecular changes. m6A may also be involved in interferon signaling and immune responses of GC.
A specific phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, was used to test the effect of PI3K inhibition on the secretion of CCL-2 in gastric cancer.
These results show that H. pylori infection induces AKT/PI3K-mediated phosphorylation of p27 at T157 and T198 to cause cytoplasmic p27 mislocalization in gastric cancer, and that p27 mislocalization is an adverse prognostic feature in gastric cancer.
Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through epidermal growth factor receptor (EGFR)-mediated PI3K/AKT and MAPK/ERK signaling pathways.
A case-control study of 1275 GC patients and 1436 controls was performed to explore the associations of potentially functional SNPs in PI3K/Akt/mTOR pathway genes with the risk of GC.
The expression of phosphatidylinositol 3' -kinase (PI3K)/ protein kinase B (AKT) and c-Jun N-terminal kinase (JNK) was down-regulated by GEN (all P < .05) while reversed by HULC overexpression.HULC was up-regulated in GC.
This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancer patients undergoing gastrectomy regardless of the PIK3CA mutation status.
Thus far, the human epidermal growth factor receptor (HER) pathway, angiogenic pathway, and phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin pathway have emerged as potential avenues for targeted therapy in AGC patients.
The mechanism analyses further found that SLC25A5-AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR-19a-3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC.
The HER-2 positive SGC-7901 secreted more transforming growth factor beta 1 (TGF-β1) and resultantly activated MMP-9 to enhance s-ICAM-1 secretion and further studies showed that phosphatidylinositol-3 kinase (PI3K)/Akt/NF-κB signaling pathway was involved in GC pathogenesis.