title: Transforming Growth Factor TGFβ Increases Levels of Microtubule-Associated Protein MAP1S and Autophagy Flux in Pancreatic Ductal Adenocarcinomas.
abstract: OBJECTIVE
  Autophagy is a cellular process to regulate the turnover of misfolded/aggregated proteins or dysfunctional organelles such as damaged mitochondria. Microtubule-associated protein MAP1S (originally named C19ORF5) is a widely-distributed homologue of neuronal-specific MAP1A and MAP1B with which autophagy marker light chain 3 (LC3) was originally co-purified. MAP1S bridges autophagic components with microtubules and mitochondria through LC3 and positively regulates autophagy flux from autophagosomal biogenesis to degradation. The MAP1S-mediated autophagy suppresses tumorigenesis as suggested in a mouse liver cancer model and in prostate cancer patients. The TGFβ signaling pathway plays a central role in pancreatic tumorigenesis, and high levels of TGFβ suggest a tumor suppressive function and predict a better survival for some patients with resectable pancreatic ductal adenocarcinoma. In this study, we try to understand the relationship between TGFβ and MAP1S-mediated autophagy in pancreatic ductal adenocarcinoma.
  
  
  METHODS
  We collected the tumor and its adjacent normal tissues from 33 randomly selected patients of pancreatic ductal adenocarcinomas to test the association between TGFβ and autophagy markers MAP1S and LC3. Then we tested the cause and effect relation between TGFβ and autophagy markers in cultured pancreatic cancer cell lines.
  
  
  RESULTS
  Here we show that levels of TGFβ and autophagy markers MAP1S and LC3 are dramatically elevated in tumor tissues from patients with pancreatic ductal adenocarcinomas. TGFβ increases levels of MAP1S protein and enhances autophagy flux.
  
  
  CONCLUSIONS
  TGFβ may suppress the development of pancreatic ductal adenocarcinomas by enhancing MAP1S-mediated autophagy.
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, 410008, Changsha, Hunan Province, China.|Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.affiliation: The First People's Hospital, Lian Yungang City, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: Fei
authors.initials: F
authors.lastname: Yue
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, United States of America.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, 410008, Changsha, Hunan Province, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Sun
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.|Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas, United States of America.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D005500:Follow-Up Studies; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C477012:MAP1LC3A protein, human; C493240:MAP1S protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta