title: Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer.
abstract: Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein associated with vascular morphogenesis and remodeling, is commonly upregulated in multiple types of human cancers and correlates with tumor progression. However, its expression pattern and underlying cellular functions in pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. In current study, we observed that expression of EDIL3 was significantly up-regulated in PDAC compared with normal controls in both cell lines and clinical specimens. In addition, elevated EDIL3 expression was positively correlated with patients' TNM stage and T classification. Kaplan-Meier analysis indicated that high EDIL3 expression was significantly associated with shorter overall survival times in PDAC patients. Multivariate Cox regression analysis confirmed EDIL3 expression, age, lymph node metastasis and histological differentiation as independent prognostic factors in PDAC. Knockdown of EDIL3 showed no significant influence on cell viability, migration, invasion and starvation-induced apoptosis, but compromised anoikis resistance and anchorage independent tumor growth of PDAC cells. Meanwhile, treatment with recombinant EDIL3 protein markedly promoted anoikis resistance and anchorage independent tumor growth. Mechanistically, we demonstrated that altered protein expression of Bcl-2 family might contribute to the oncogenic activities of EDIL3. In conclusion, this study provides evidences that EDIL3 is a potential predictor and plays an important role in anchorage independent tumor growth of PDAC and EDIL3-related pathways might represent a novel therapeutic strategy for treatment of pancreatic cancer.
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, P.R. China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Shu-Heng
authors.initials: SH
authors.lastname: Jiang
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, P.R. China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.|Department of Urology, Shanghai No.5 People's Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ming-Xuan
authors.initials: MX
authors.lastname: Feng
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, P.R. China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Guang-Ang
authors.initials: GA
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, P.R. China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Cao
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Yan-Miao
authors.initials: YM
authors.lastname: Huo
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Yang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xue-Liang
authors.initials: XL
authors.lastname: Fu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
authors.forename: Shan-Yun
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, P.R. China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Jian-Ren
authors.initials: JR
authors.lastname: Gu
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory of Oncogene and Related Genes, Shanghai Jiao-Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; D012333:RNA, Messenger
keywords: EDIL3; anoikis; pancreatic cancer; prognosis; tumor growth