title: DEPTOR suppresses the progression of esophageal squamous cell carcinoma and predicts poor prognosis.
abstract: As a naturally occurring inhibitor of mTOR, accumulated evidence has suggested that DEPTOR plays a pivotal role in suppressing the progression of human malignances. However, the function of DEPTOR in the development of esophageal squamous cell carcinoma (ESCC) is still unclear. Here we report that the expression of DEPTOR is significantly reduced in tumor tissues derived from human patients with ESCC, and the downregulation of DEPTOR predicts a poor prognosis of ESCC patients. In addition, we found that the expression of DEPTOR negatively regulates the tumorigenic activities of ESCC cell lines (KYSE150, KYSE510 and KYSE190). Furthermore, ectopic DEPTOR expression caused a significant suppression of the cellular proliferation, migration and invasion of KYSE150 cells, which has the lowest expression level of DEPTOR in the three cell lines. Meanwhile, CRISPR/Cas9 mediated knockout of DEPTOR in KYSE-510 cells significantly promoted cellular proliferation, migration and invasion. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic DEPTOR expression as compared to untreated KYSE150 cells, and was markedly enhanced in DEPTOR knockout KYSE-510 cells. Biochemical studies revealed that overexpression of DEPTOR led to the suppression of AKT/mTOR pathway as evidenced by reduced phosphorylation of AKT, mTOR and downstream SGK1, indicating DEPTOR might control the progression of ESCC through AKT/mTOR signaling pathway. Thus, these findings, for the first time, demonstrated that DEPTOR inhibits the tumorigenesis of ESCC cells and might serve as a potential therapeutic target or prognostic marker for human patients with ESCC.
authors.affiliation: Department of Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Ji
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Sheng-Bao
authors.initials: SB
authors.lastname: Li
authors.affiliation: Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Kuncheng
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C556139:DEPTOR protein, human; C546842:MTOR protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: DEPTOR; esophageal squamous cell carcinoma; mTOR; proliferation