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Article Open Access

FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1

  • Authors:
    • Qiangsheng Hu
    • Yi Qin
    • Bo Zhang
    • Chen Liang
    • Shunrong Ji
    • Si Shi
    • Wenyan Xu
    • Jinfeng Xiang
    • Dingkong Liang
    • Quanxing Ni
    • Xianjun Yu
    • Jin Xu
  • View Affiliations / Copyright

    Affiliations: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2069-2077
    |
    Published online on: July 28, 2017
       https://doi.org/10.3892/or.2017.5856
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Hu Q, Qin Y, Zhang B, Liang C, Ji S, Shi S, Xu W, Xiang J, Liang D, Ni Q, Ni Q, et al: FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1. Oncol Rep 38: 2069-2077, 2017.
APA
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S. ... Xu, J. (2017). FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1. Oncology Reports, 38, 2069-2077. https://doi.org/10.3892/or.2017.5856
MLA
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S., Xu, W., Xiang, J., Liang, D., Ni, Q., Yu, X., Xu, J."FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1". Oncology Reports 38.4 (2017): 2069-2077.
Chicago
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S., Xu, W., Xiang, J., Liang, D., Ni, Q., Yu, X., Xu, J."FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1". Oncology Reports 38, no. 4 (2017): 2069-2077. https://doi.org/10.3892/or.2017.5856
Copy and paste a formatted citation
x
Spandidos Publications style
Hu Q, Qin Y, Zhang B, Liang C, Ji S, Shi S, Xu W, Xiang J, Liang D, Ni Q, Ni Q, et al: FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1. Oncol Rep 38: 2069-2077, 2017.
APA
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S. ... Xu, J. (2017). FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1. Oncology Reports, 38, 2069-2077. https://doi.org/10.3892/or.2017.5856
MLA
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S., Xu, W., Xiang, J., Liang, D., Ni, Q., Yu, X., Xu, J."FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1". Oncology Reports 38.4 (2017): 2069-2077.
Chicago
Hu, Q., Qin, Y., Zhang, B., Liang, C., Ji, S., Shi, S., Xu, W., Xiang, J., Liang, D., Ni, Q., Yu, X., Xu, J."FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine through upregulation of ENT1". Oncology Reports 38, no. 4 (2017): 2069-2077. https://doi.org/10.3892/or.2017.5856
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