title: Reciprocal Negative Regulation between EGFR and DEPTOR Plays an Important Role in the Progression of Lung Adenocarcinoma.
abstract: The epidermal growth factor receptor (EGFR) activates downstream mTOR phosphorylation to promote the progression of many different tumor types, thus making it a prime therapeutic target. However, the role of DEP domain-containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, remains unclear in this process. Here, it is reported that EGFR expression is significantly increased in tumors of lung adenocarcinoma patients and is negatively correlated with the expression of DEPTOR. Activation of EGFR signaling, by EGF, in A549 lung adenocarcinoma cells (overexpressing EGFR) significantly enhanced the function of the mTOR autoamplification loop, consisting of S6K, mTOR, CK1α, and βTrCP1, which resulted in downregulation of DEPTOR expression. Gefitinib, a specific EGFR inhibitor, stimulated DEPTOR accumulation by downregulating the function of the mTOR autoamplification loop. Furthermore, a series of assays conducted in DEPTOR knockout or ectopic expression in A549 cells confirmed that DEPTOR inhibited proliferation, migration, and invasion as well as the in vivo tumor growth of lung adenocarcinoma. Importantly, tumor progression mediated by EGFR ectopic expression was diminished by transfection with DEPTOR. This study uncovers the important inhibitory role of DEPTOR in lung adenocarcinoma progression and reveals a novel mechanism that EGFR downregulates DEPTOR expression to facilitate tumor growth.
  
  
  
  DEPTOR acts as a tumor suppressor by limiting EGFR-driven lung adenocarcinoma progression. Mol Cancer Res; 14(5); 448-57. ©2016 AACR.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China.
authors.forename: Jialong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Pan
authors.affiliation: Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio. Hua.Zhu@osumc.edu zresearch@sohu.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China. Hua.Zhu@osumc.edu zresearch@sohu.com.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C556139:DEPTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors