Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture.
<b>Conclusions</b>: Our data demonstrate that vitamin C kills thyroid cancer cells by inhibiting MAPK/ERK and PI3K/AKT pathways via a ROS-dependent mechanism and suggest that pharmaceutical concentration of vitamin C has potential clinical use in thyroid cancer therapy.
Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment.
In conclusion, the data of this study suggested that naringin presented anti-tumor effects in TC cells through inhibiting TC cell proliferation and inducing cell apoptosis via regulating the expression of cell proliferation and apoptosis related genes and PI3K/AKT pathway activation.
PPFP thyroid cancers have increased activation of AKT, and mice with thyroid-specific expression of PPFP combined with thyroid-specific loss of PTEN (a negative regulator of AKT) develop thyroid cancer.
As phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a fundamental oncogenic driver in many thyroid cancers, we explored a potential role for miR-146b and its target genes in PI3K/AKT activation.
Interestingly, the exposure of thyroid carcinoma cells to PLX4032 resulted in a rapid feedback activation of EGFR signaling with parallel activation of AKT phosphorylation.
Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response.<b>Experimental Design:</b> CUDC-907 is a first-in-class compound, functioning as a dual inhibitor of HDACs and the PI3K/AKT pathway.
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer.
Increased activation of alternative proliferation pathways (as determined by the increase of AKT kinase activity) counteracts the effect of BRAF kinase inhibition in thyroid carcinomas.
The aim of this study is to identify its expression, function, and molecular mechanism in thyroid cancer. microRNA-137 (miR-137) downregulation was observed in thyroid cancer tissues compared with normal thyroid tissues. miR-137 mimics downregulated B-CPAP cell proliferation, colony formation ability, and invasion, with suppressed expression of cyclin E, MMP2, p-ERK, and p-AKT. miR-137 inhibitor transfection in TPC-1 cell line showed the opposite effects.
In this review article, the role of different signaling pathways of PI3K/AKT in thyroid cancers, with the emphasis on the PI3K/AKT/mammalian target of rapamycin (mTOR), PI3K/AKT/forkhead box O (FOXO) and PI3K/AKT/phosphatase and tensin homolog deleted on chromosome ten (PTEN) pathways, and various therapeutic strategies targeting these pathways have been summarized.
In these cell lines, both active ERK and active AKT kinase proteins were found in BRAF V600E mutated thyroid carcinoma cells by immunofluorescent staining and Western blots experiments.
MicroRNA-126 suppresses proliferation of undifferentiated (BRAF(V600E) and BRAF(WT)) thyroid carcinoma through targeting PIK3R2 gene and repressing PI3K-AKT proliferation-survival signalling pathway.
Taken together, these results suggest that knockdown of HPIP inhibits the proliferation, migration and EMT by suppressing the PI3K/AKT pathway, and HPIP may be a potential therapeutic target for the treatment of thyroid carcinoma.