PLX116430

GSE79400: Digitalis-like compounds facilitate redifferentiation of non-medullary thyroid cancer through intracellular Ca2+, cFOS and autophagy dependent pathways

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

About 20-30% of patients with metastatic non-medullary thyroid cancer (TC) have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodine therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activation for redifferentiation in thyroid cancer cell lines. Five, all digitalis-like compounds, restored hNIS expression and iodine uptake in TC cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and cFOS activation. Cell proliferation was inhibited by downregulating Akt1 and by induction of autophagy and p21-dependent cell cycle arrest. All together, digitalis-like compounds could represent a promising treatment modality for patients with dedifferentiated TC. SOURCE: Theo,S,Plantinga (theo.plantinga@radboudumc.nl) - Radboud University Medical Center