GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies

Weixing Dai, Ye Xu, Shaobo Mo, Qingguo Li, Jun Yu, Renjie Wang, Yanlei Ma, Yan Ni, Wenqiang Xiang, Lingyu Han, Long Zhang, Sanjun Cai, Jun Qin, Wen Lian Chen, Wei JIA, Guoxiang Cai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Cancer cells are usually characterized by hyperactive glucose metabolism, which can often lead to glucose scarcity; thus, alternative pathways to rewire cancer metabolism are required. Here, we demonstrated that GLUT3 was highly expressed in colorectal cancer (CRC) and negatively linked to CRC patient outcomes, whereas GLUT1 was not associated with CRC prognosis. Under glucose-limiting conditions, GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis. Notably, GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress. Mechanistically, low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway. Furthermore, high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens. Together, the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.

Original languageEnglish
Article number177
JournalSignal Transduction and Targeted Therapy
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Scopus Subject Areas

  • Genetics
  • Cancer Research

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