Figure 14
From: Thapsigargin sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation
Schematic diagram of thapsigargin-stimulated TRAIL-induced apoptosis in human ESCC.
ER stress response could effectively sensitize human esophageal cancer to TRAIL-mediated apoptosis via TRAILRs and AMPK pathway. Details are as follows: ① Induction of ER stress with thapsigargin increases the CHOP expression, and then CHOP upregulates DR5 by combining to CHOP-binding site. Upregulation of DR5 improves the receptor number which could bond more TRAIL in ESCC cells. ② TRAIL/DR5 binding induced ESCC cells apoptosis mediated by ROS via AMPK phosphorylation. ③ Induction of ER stress can directly activate AMPK phosphorylation, which play an efficient role against ESCC cells. ESCC, esophageal squamous cell carcinoma; THA, thapsigargin; ERS, endoplasmic reticulum stress; CHOP, C/EBP-homologous protein; DR5 (i.e., Apo2), death receptor 5; TRAIL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand; AMPK, adenosine monophosphate activated protein kinase; ROS, reactive oxygen species.
