Obg-like ATPase 1 exacerbated gemcitabine drug resistance of pancreatic cancer

Autor: Jianzhou Liu, Jing Huang, Jun Lu, Runze Ouyang, Wenchao Xu, Jianlu Zhang, Kevin Chen-Xiao, Chengjun Wu, Dong Shang, Vay Liang W(Bill) Go, Junchao Guo, Gary Guishan Xiao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 110027- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.110027
Popis: Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis due to inefficient diagnosis and tenacious drug resistance. Obg-like ATPase 1 (OLA1) is overexpressed in many malignant tumors. The molecular mechanism of OLA1 underlying gemcitabine (GEM)-induced drug resistance was investigated in this study. An enhanced expression of OLA1 was observed in a GEM acquired resistant pancreatic cancer cell lines and in patients with pancreatic cancer. Overexpressed OLA1 showed poor overall survival rates in patients with pancreatic cancer. Dysregulation of the OLA1 reduced expression of CD44+/CD133+, and improved the sensitivity of pancreatic cancer cells to GEM. OLA1 highly expression facilitated the formation of the OLA1/Sonic Hedgehog (SHH)/Hedgehog-interacting protein (HHIP) complex in nuclei, resulting in the inhibition of negative feedback of Hedgehog signaling induced by HHIP. This study suggests that OLA1 may be developed as an innovative drug target for an effective therapy of pancreatic cancer.
Databáze: Directory of Open Access Journals