Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer
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Shu-Heng Jiang1,2,*, Yang Wang1,2,4,*, Jian-Yu Yang3,*, Jun Li2,*, Ming-Xuan Feng5, Ya-Hui Wang1,2, Xiao-Mei Yang2, Ping He2, Guang-Ang Tian2, Xiao-Xin Zhang2, Qing Li1,2, Xiao-Yan Cao2, Yan-Miao Huo3, Min-Wei Yang3, Xue-Liang Fu3, Jiao Li3, De-Jun Liu3, Miao Dai7, Shan-Yun Wen7, Jian-Ren Gu1,2, Jie Hong6, Rong Hua3, Zhi-Gang Zhang2, Yong-Wei Sun3
1Shanghai Medical College of Fudan University, Shanghai, P.R. China
2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China
3Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China
4Department of Urology, Shanghai No.5 People’s Hospital, Fudan University, Shanghai, P.R. China
5Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China
6Division 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
7Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, P.R. China
*These authors contributed equally to this work
Yong-Wei Sun, e-mail: [email protected]
Zhi-Gang Zhang, e-mail: [email protected]
Rong Hua, e-mail: [email protected]
Jie Hong, e-mail: [email protected]
Keywords: EDIL3, prognosis, tumor growth, anoikis, pancreatic cancer
Received: June 16, 2015 Accepted: November 28, 2015 Published: December 28, 2015
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.
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