title: ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin.
abstract: The ETS family transcription factor ESE3 is a crucial element in differentiation and development programs for many epithelial tissues. Here we report its role as a tumor suppressor in pancreatic cancer. We observed drastically lower ESE3 expression in pancreatic ductal adenocarcinomas (PDAC) compared with adjacent normal pancreatic tissue. Reduced expression of ESE3 in PDAC correlated closely with an increase in lymph node metastasis and vessel invasion and a decrease in relapse-free and overall survival in patients. In functional experiments, downregulating the expression of ESE3 promoted PDAC cell motility and invasiveness along with metastasis in an orthotopic mouse model. Mechanistic studies in PDAC cell lines, the orthotopic mouse model, and human PDAC specimens demonstrated that ESE3 inhibited PDAC metastasis by directly upregulating E-cadherin expression at the level of its transcription. Collectively, our results establish ESE3 as a negative regulator of PDAC progression and metastasis by enforcing E-cadherin upregulation.Cancer Res; 77(4); 874-85. ©2016 AACR.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.|Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Tiansuo
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Xiuchao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: Chongbiao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P.R. China.
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.affiliation: Department of Tumor Biology and Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Shengyu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas. kepxie@mdanderson.org haojihui@tjmuch.com renhe@tjmuch.com.
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, P.R. China. kepxie@mdanderson.org haojihui@tjmuch.com renhe@tjmuch.com.
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000077209:Decitabine; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C403306:EHF protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine