Obg-like ATPase 1 exacerbated gemcitabine drug resistance of pancreatic cancer
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
Affiliations
Jianzhou Liu
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China; Institute of clinical medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Jing Huang
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China
Jun Lu
Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
Runze Ouyang
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
Wenchao Xu
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Jianlu Zhang
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Kevin Chen-Xiao
Department of Nutritional Sciences and Toxicology, University of California Berkeley, San Francisco, CA, USA
Chengjun Wu
School of Biomedical Engineering, Dalian University of Technology, Dalian, China
Dong Shang
Department of General Surgery, Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
Vay Liang W(Bill) Go
The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Junchao Guo
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Corresponding author
Gary Guishan Xiao
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China; The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA; Corresponding author
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.
