Unfolded protein response (UPR) protects malignant cells from endoplasmic reticulum stress-induced apoptosis. We report that
Aurora kinase A (
AURKA) promotes
cancer cell survival by activating UPR in esophageal
adenocarcinoma (EAC). A strong positive correlation between
AURKA and binding
immunoglobulin protein (BIP)
mRNA expression levels was found in EACs. The in vitro assays indicated that
AURKA promoted IRE1α
protein phosphorylation, activating prosurvival UPR in FLO-1 and OE33 cells. The use of acidic
bile salts to mimic reflux conditions in patients induced high
AURKA and IRE1α levels. This induction was abrogated by
AURKA knockdown in EAC cells.
AURKA and p-IRE1α
protein colocalization was observed in neoplastic gastroesophageal lesions of the L2-IL1b mouse model of Barrett's esophageal
neoplasia. The combined treatment using
AURKA inhibitor and
tunicamycin synergistically induced
cancer cell death. The use of
alisertib for
AURKA inhibition in the EAC xenograft model led to a decrease in IRE1α phosphorylation with a significant reduction in
tumor growth. These results indicate that
AURKA activates UPR, promoting
cancer cell survival during ER stress in EAC. Targeting
AURKA can significantly reverse prosurvival UPR signaling mechanisms and decrease
cancer cell survival, providing a promising approach for the treatment of EAC patients.