TY - JOUR
T1 - GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies
AU - Dai, Weixing
AU - Xu, Ye
AU - Mo, Shaobo
AU - Li, Qingguo
AU - Yu, Jun
AU - Wang, Renjie
AU - Ma, Yanlei
AU - Ni, Yan
AU - Xiang, Wenqiang
AU - Han, Lingyu
AU - Zhang, Long
AU - Cai, Sanjun
AU - Qin, Jun
AU - Chen, Wen Lian
AU - Jia, Wei
AU - Cai, Guoxiang
N1 - Funding Information:
We thank the TCGA and GEO database for providing their platforms and contributors for their valuable data sets. This study was supported by the Grant of National Natural Science Foundation of China (No. 81871958 and No. 81572351) and Grant of Science and Technology Commission of Shanghai Municipality (No. 16401970502 and No.17411951100 and No. 19140902100).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41392-020-00220-9
DO - 10.1038/s41392-020-00220-9
M3 - Article
C2 - 32873793
AN - SCOPUS:85090026092
SN - 2095-9907
VL - 5
JO - Signal Transduction and Targeted Therapy
JF - Signal Transduction and Targeted Therapy
IS - 1
M1 - 177
ER -