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Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826201/ https://www.ncbi.nlm.nih.gov/pubmed/26735172 http://dx.doi.org/10.18632/oncotarget.6772 |
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author | Jiang, Shu-Heng Wang, Yang Yang, Jian-Yu Li, Jun Feng, Ming-Xuan Wang, Ya-Hui Yang, Xiao-Mei He, Ping Tian, Guang-Ang Zhang, Xiao-Xin Li, Qing Cao, Xiao-Yan Huo, Yan-Miao Yang, Min-Wei Fu, Xue-Liang Li, Jiao Liu, De-Jun Dai, Miao Wen, Shan-Yun Gu, Jian-Ren Hong, Jie Hua, Rong Zhang, Zhi-Gang Sun, Yong-Wei |
author_facet | Jiang, Shu-Heng Wang, Yang Yang, Jian-Yu Li, Jun Feng, Ming-Xuan Wang, Ya-Hui Yang, Xiao-Mei He, Ping Tian, Guang-Ang Zhang, Xiao-Xin Li, Qing Cao, Xiao-Yan Huo, Yan-Miao Yang, Min-Wei Fu, Xue-Liang Li, Jiao Liu, De-Jun Dai, Miao Wen, Shan-Yun Gu, Jian-Ren Hong, Jie Hua, Rong Zhang, Zhi-Gang Sun, Yong-Wei |
author_sort | Jiang, Shu-Heng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4826201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48262012016-05-09 Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer Jiang, Shu-Heng Wang, Yang Yang, Jian-Yu Li, Jun Feng, Ming-Xuan Wang, Ya-Hui Yang, Xiao-Mei He, Ping Tian, Guang-Ang Zhang, Xiao-Xin Li, Qing Cao, Xiao-Yan Huo, Yan-Miao Yang, Min-Wei Fu, Xue-Liang Li, Jiao Liu, De-Jun Dai, Miao Wen, Shan-Yun Gu, Jian-Ren Hong, Jie Hua, Rong Zhang, Zhi-Gang Sun, Yong-Wei Oncotarget Research Paper 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. Impact Journals LLC 2015-12-28 /pmc/articles/PMC4826201/ /pubmed/26735172 http://dx.doi.org/10.18632/oncotarget.6772 Text en Copyright: © 2016 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jiang, Shu-Heng Wang, Yang Yang, Jian-Yu Li, Jun Feng, Ming-Xuan Wang, Ya-Hui Yang, Xiao-Mei He, Ping Tian, Guang-Ang Zhang, Xiao-Xin Li, Qing Cao, Xiao-Yan Huo, Yan-Miao Yang, Min-Wei Fu, Xue-Liang Li, Jiao Liu, De-Jun Dai, Miao Wen, Shan-Yun Gu, Jian-Ren Hong, Jie Hua, Rong Zhang, Zhi-Gang Sun, Yong-Wei Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title | Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title_full | Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title_fullStr | Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title_full_unstemmed | Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title_short | Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
title_sort | overexpressed edil3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826201/ https://www.ncbi.nlm.nih.gov/pubmed/26735172 http://dx.doi.org/10.18632/oncotarget.6772 |
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