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High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer

BACKGROUND: Diabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship b...

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Autores principales: Zhou, Cancan, Qian, Weikun, Li, Jie, Ma, Jiguang, Chen, Xin, Jiang, Zhengdong, Cheng, Liang, Duan, Wanxing, Wang, Zheng, Wu, Zheng, Ma, Qingyong, Li, Xuqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625066/
https://www.ncbi.nlm.nih.gov/pubmed/31296258
http://dx.doi.org/10.1186/s13046-019-1288-7
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author Zhou, Cancan
Qian, Weikun
Li, Jie
Ma, Jiguang
Chen, Xin
Jiang, Zhengdong
Cheng, Liang
Duan, Wanxing
Wang, Zheng
Wu, Zheng
Ma, Qingyong
Li, Xuqi
author_facet Zhou, Cancan
Qian, Weikun
Li, Jie
Ma, Jiguang
Chen, Xin
Jiang, Zhengdong
Cheng, Liang
Duan, Wanxing
Wang, Zheng
Wu, Zheng
Ma, Qingyong
Li, Xuqi
author_sort Zhou, Cancan
collection PubMed
description BACKGROUND: Diabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship between high glucose microenvironment, SREBP1 and pancreatic cancer remains to be explored. METHODS: Clinical data and surgical specimens were collected. Pancreatic cancer cell lines BxPc-3 and MiaPaCa-2 were cultured in specified medium. Immunohistochemistry (IHC) and western blotting were performed to detect the expression of SREBP1. MTT and colony formation assays were applied to investigate cell proliferation. Immunofluorescence, mRFP-GFP adenoviral vector and transmission electron microscopy were performed to evaluate autophagy. We used streptozotocin (STZ) to establish a high glucose mouse model for the in vivo study. RESULTS: We found that high blood glucose levels were associated with poor prognosis in pancreatic cancer patients. SREBP1 was overexpressed in both pancreatic cancer tissues and pancreatic cancer cell lines. High glucose microenvironment promoted tumor proliferation, suppressed apoptosis and inhibited autophagy level by enhancing SREBP1 expression. In addition, activation of autophagy accelerated SREBP1 expression and suppressed apoptosis. Moreover, high glucose promotes tumor growth in vivo by enhancing SREBP1 expression. CONCLUSION: Our results indicate that SREBP1-autophagy axis plays a crucial role in tumor progression induced by high glucose microenvironment. SREBP1 may represent a novel target for pancreatic cancer prevention and treatment.
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spelling pubmed-66250662019-07-23 High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer Zhou, Cancan Qian, Weikun Li, Jie Ma, Jiguang Chen, Xin Jiang, Zhengdong Cheng, Liang Duan, Wanxing Wang, Zheng Wu, Zheng Ma, Qingyong Li, Xuqi J Exp Clin Cancer Res Research BACKGROUND: Diabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship between high glucose microenvironment, SREBP1 and pancreatic cancer remains to be explored. METHODS: Clinical data and surgical specimens were collected. Pancreatic cancer cell lines BxPc-3 and MiaPaCa-2 were cultured in specified medium. Immunohistochemistry (IHC) and western blotting were performed to detect the expression of SREBP1. MTT and colony formation assays were applied to investigate cell proliferation. Immunofluorescence, mRFP-GFP adenoviral vector and transmission electron microscopy were performed to evaluate autophagy. We used streptozotocin (STZ) to establish a high glucose mouse model for the in vivo study. RESULTS: We found that high blood glucose levels were associated with poor prognosis in pancreatic cancer patients. SREBP1 was overexpressed in both pancreatic cancer tissues and pancreatic cancer cell lines. High glucose microenvironment promoted tumor proliferation, suppressed apoptosis and inhibited autophagy level by enhancing SREBP1 expression. In addition, activation of autophagy accelerated SREBP1 expression and suppressed apoptosis. Moreover, high glucose promotes tumor growth in vivo by enhancing SREBP1 expression. CONCLUSION: Our results indicate that SREBP1-autophagy axis plays a crucial role in tumor progression induced by high glucose microenvironment. SREBP1 may represent a novel target for pancreatic cancer prevention and treatment. BioMed Central 2019-07-11 /pmc/articles/PMC6625066/ /pubmed/31296258 http://dx.doi.org/10.1186/s13046-019-1288-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhou, Cancan
Qian, Weikun
Li, Jie
Ma, Jiguang
Chen, Xin
Jiang, Zhengdong
Cheng, Liang
Duan, Wanxing
Wang, Zheng
Wu, Zheng
Ma, Qingyong
Li, Xuqi
High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title_full High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title_fullStr High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title_full_unstemmed High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title_short High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
title_sort high glucose microenvironment accelerates tumor growth via srebp1-autophagy axis in pancreatic cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625066/
https://www.ncbi.nlm.nih.gov/pubmed/31296258
http://dx.doi.org/10.1186/s13046-019-1288-7
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