UPP1 enhances bladder cancer progression and gemcitabine resistance through AKT
Wenzhi Du, Sheng Tu, Wenxiu Zhang, Yi Zhang, Wei Liu, Kangping Xiong, Fenfang Zhou, Na Li, Renjie Zhang, Jingtian Yu, Mingxing Li, Wan Xiang, Kaiyu Qian, Gang Wang, Yu Xiao, Xinghuan Wang, Lingao Ju
Abstract
. Additionally, UPP1 promoted AKT activation by facilitating the binding of AKT to PDK1 and PDK2 and the recruitment of phosphatidylinositol 3,4,5-triphosphate to AKT. Moreover, the beneficial effects of UPP1 on BLCA tumorigenesis were mitigated upon UPP1 mutation with Arg94 or MK2206 treatment (AKT-specific inhibitor). AKT overexpression or SC79 (AKT-specific activator) treatment restored tumor malignancy and drug resistance. Thus, this study revealed that UPP1 is a crucial oncogene and a potential therapeutic target for BLCA and that UPP1 activates the AKT signaling pathway and enhances tumorigenesis and drug resistance to gemcitabine.