title: Different functions of DEPTOR in modulating sensitivity to chemotherapy for esophageal squamous cell carcinoma.
abstract: There have been paradoxical findings regarding the expression of DEP domain-containing mTOR-interacting protein (DEPTOR) and its role in predicting prognosis in esophageal squamous cell carcinoma (ESCC). Here we show that DEPTOR expression was significantly increased in tumor tissues and predicted good survival in early stage ESCC patients but not in advanced stage patients. In vitro，our studies showed that ESCC cell lines could be classified into relatively high and low DEPTOR-expressing subgroups according to esophageal squamous epithelial cell line Het-1A.In our study, different levels of DEPTOR expression absolutely determined the response to chemotherapy. In relatively low-expressing cell lines, DEPTOR increased chemotherapy sensitivity via deactivation of the AKT pathway. In relatively high-expressing cell lines, DEPTOR increased cell survival and chemoresistance by strong feedback activation of the IRS1-PI3K-AKT-survivin pathway that occurred after downregulation of ribosomal protein S6 kinase (S6K). Collectively, our findings highlight the dichotomous nature of DEPTOR functions in modulating chemotherapy sensitivity in different ESCC cells.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zelong
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
authors.forename: Wanfu
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Junmeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Bioinformatics, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Thoracic surgery, Nanfang Hospital, Southern Medical University, Guangzhou510515, Guangdong, China.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Thoracic surgery, Nanfang Hospital, Southern Medical University, Guangzhou510515, Guangdong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Thoracic surgery, Nanfang Hospital, Southern Medical University, Guangzhou510515, Guangdong, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Diao
authors.affiliation: Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: nmjiachunhong@163.com.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: zhengh001@163.com.
authors.forename: Hang
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077022:Survivin; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel; C556139:DEPTOR protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Chemoresistance; DEPTOR; Esophageal squamous cell carcinoma; IRS1-PI3K-AKT-survivin