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FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1
F-box and WD repeat domain-containing 7 (FBW7) has been characterized as a tumor suppressor, and its mutation or decreased expression has been observed in many types of human cancers. Our recent studies have uncovered that in pancreatic cancer, the KRAS mutation decreased FBW7 expression through pho...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652962/ https://www.ncbi.nlm.nih.gov/pubmed/28765935 http://dx.doi.org/10.3892/or.2017.5856 |
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author | Hu, Qiangsheng Qin, Yi Zhang, Bo Liang, Chen Ji, Shunrong Shi, Si Xu, Wenyan Xiang, Jinfeng Liang, Dingkong Ni, Quanxing Yu, Xianjun Xu, Jin |
author_facet | Hu, Qiangsheng Qin, Yi Zhang, Bo Liang, Chen Ji, Shunrong Shi, Si Xu, Wenyan Xiang, Jinfeng Liang, Dingkong Ni, Quanxing Yu, Xianjun Xu, Jin |
author_sort | Hu, Qiangsheng |
collection | PubMed |
description | F-box and WD repeat domain-containing 7 (FBW7) has been characterized as a tumor suppressor, and its mutation or decreased expression has been observed in many types of human cancers. Our recent studies have uncovered that in pancreatic cancer, the KRAS mutation decreased FBW7 expression through phosphorylation and subsequent ubiquitination. Moreover, FBW7 inhibited aerobic glycolysis in pancreatic cancer via induction of thioredoxin-interacting protein (TXNIP), a mitochondrial localized tumor suppressor. The roles of FBW7 in anti-apoptosis and drug resistance via proteosomal degradation of myeloid cell leukemia-1 (MCL-1), which is an anti-apoptotic factor have been reported. However, the role of FBW7 in the chemotherapeutic resistance of pancreatic cancer to gemcitabine has seldom been reported. In the present study, we demonstrated that overexpression of FBW7 in pancreatic cancer cells rendered increased sensitivity to gemcitabine. Mechanistically, FBW7 promoted gemcitabine sensitivity via upregulation of equilibrative nucleoside transporter 1 (ENT1) at the protein level rather than the transcriptional level. In depth analysis demonstrated that the ENT1 protein level could be increased by lysosome inhibition. Taken together, our results demonstrated that FBW7 could be a target for improving the therapeutic efficacy of gemcitabine by induction of ENT1. |
format | Online Article Text |
id | pubmed-5652962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-56529622017-11-02 FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 Hu, Qiangsheng Qin, Yi Zhang, Bo Liang, Chen Ji, Shunrong Shi, Si Xu, Wenyan Xiang, Jinfeng Liang, Dingkong Ni, Quanxing Yu, Xianjun Xu, Jin Oncol Rep Articles F-box and WD repeat domain-containing 7 (FBW7) has been characterized as a tumor suppressor, and its mutation or decreased expression has been observed in many types of human cancers. Our recent studies have uncovered that in pancreatic cancer, the KRAS mutation decreased FBW7 expression through phosphorylation and subsequent ubiquitination. Moreover, FBW7 inhibited aerobic glycolysis in pancreatic cancer via induction of thioredoxin-interacting protein (TXNIP), a mitochondrial localized tumor suppressor. The roles of FBW7 in anti-apoptosis and drug resistance via proteosomal degradation of myeloid cell leukemia-1 (MCL-1), which is an anti-apoptotic factor have been reported. However, the role of FBW7 in the chemotherapeutic resistance of pancreatic cancer to gemcitabine has seldom been reported. In the present study, we demonstrated that overexpression of FBW7 in pancreatic cancer cells rendered increased sensitivity to gemcitabine. Mechanistically, FBW7 promoted gemcitabine sensitivity via upregulation of equilibrative nucleoside transporter 1 (ENT1) at the protein level rather than the transcriptional level. In depth analysis demonstrated that the ENT1 protein level could be increased by lysosome inhibition. Taken together, our results demonstrated that FBW7 could be a target for improving the therapeutic efficacy of gemcitabine by induction of ENT1. D.A. Spandidos 2017-10 2017-07-28 /pmc/articles/PMC5652962/ /pubmed/28765935 http://dx.doi.org/10.3892/or.2017.5856 Text en Copyright: © Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Hu, Qiangsheng Qin, Yi Zhang, Bo Liang, Chen Ji, Shunrong Shi, Si Xu, Wenyan Xiang, Jinfeng Liang, Dingkong Ni, Quanxing Yu, Xianjun Xu, Jin FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title | FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title_full | FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title_fullStr | FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title_full_unstemmed | FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title_short | FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1 |
title_sort | fbw7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ent1 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652962/ https://www.ncbi.nlm.nih.gov/pubmed/28765935 http://dx.doi.org/10.3892/or.2017.5856 |
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