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An essential role for GLUT5-mediated fructose utilization in exacerbating the malignancy of clear cell renal cell carcinoma

  • Xing Jin
  • Yupei Liang
  • Dan Liu
  • Qin Luo
  • Lili Cai
  • Jia Wu
  • Lijun JiaEmail author
  • Wen-Lian ChenEmail author
Original Article
  • 54 Downloads

Abstract

Fructose is an important alternative carbon source for several tumors, and GLUT5 is the major fructose transporter which mediates most of fructose uptake in cells. So far, it is unclear whether GLUT5-mediated fructose utilization is important for clear cell renal cell carcinoma (ccRCC). Here, we demonstrated that GLUT5 was highly expressed in a panel of ccRCC cell lines. High GLUT5 expression exacerbated the neoplastic phenotypes of ccRCC cells, including cell proliferation and colony formation. On the other hand, deletion of the GLUT5-encoding gene SLC2A5 dramatically attenuated cellular malignancy via activating the apoptotic pathway. Moreover, administration of 2,5-anhydro-D-mannitol (2,5-AM), a competitive inhibitor of fructose uptake, could markedly suppress ccRCC cell growth. Together, we provide a new mechanistic insight for GLUT5-mediated fructose utilization in ccRCC cells and highlight the therapeutic potential for targeting this metabolic pathway against ccRCC.

Keywords

Clear cell renal cell carcinoma GLUT5 Fructose 

Notes

Author contributions

Conceptualization: L.J. and W.-L.C.; study supervision: L.J. and W.-L.C.; molecular and cellular experiments: X.J., Y.L., D.L., Q.L., L.C., and J.W.; statistical analysis: X.J. and Y.L.; writing—original draft: X.J.; writing—review & editing: L.J. and W.-L.C.

Funding

This study is supported by the Chinese Minister of Science and Technology grant (2016YFA0501800), National Natural Science Foundation of China (Grant Nos. 81625018, 81770147, 81802891), Program of Shanghai Academic/Technology Research Leader (18XD1403800), National Thirteenth Five-Year Science and Technology Major Special Project for New Drug and Development (2017ZX09304001), The National Scientific and Technological Major Special Project of China (2018ZX09201008-002), Shanghai Rising-Star Program (18QA1404100), Research fund of Shanghai Municipal Commission of Health (20174Y0090), Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Youth Talent Program, Gaofeng Clinical Medicine Grant of Shanghai Municipal Education Commission, and Xinling Scholar Program of Shanghai University of Traditional Chinese Medicine.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Supplementary material

10565_2019_9478_MOESM1_ESM.docx (182 kb)
ESM 1 (DOCX 182 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Cancer InstituteFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Cancer Institute, Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  3. 3.Department of Immunology, School of Basic Medical SciencesFudan UniversityShanghaiChina

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