title: Inhibition of the Hedgehog pathway induces autophagy in pancreatic ductal adenocarcinoma cells.
abstract: The HH signaling pathway is a 'core' signal transduction pathway in pancreatic cancer that promotes the tumorigenesis of pancreatic cancers via enhancing cell proliferation, increasing invasion and metastasis and protecting against apoptosis. In the present study, we found that HH signaling regulates autophagy in pancreatic cancer cells. Activation of HH signaling inhibits autophagy, while inhibition of the HH pathway induces autophagy. Although the role of autophagy in cell survival and apoptosis may depend on tumor type and the microenvironment, our data clearly demonstrated that GANT61-induced autophagy contributed to reduced viability and increased apoptosis in pancreatic cancer cells both in vivo and in vitro, and these effects were reversed by the autophagy inhibitor, 3-MA. We propose that HH signaling by regulating autophagy plays an important role in determining the cellular response to HH-targeted therapy in pancreatic cancer and further investigation of the interaction between autophagy and HH signaling is particularly important.
authors.affiliation: Department of General Surgery, Fourth Affiliated Hospital of Nantong University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Hepatobiliary Surgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Fourth Affiliated Hospital of Nantong University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, P.R. China.
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Zha
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D005260:Female; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: C551027:GANT 61; C400551:GLI1 protein, human; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011725:Pyridines; D011743:Pyrimidines; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2