FUT3 mediated GRP78 fucosylation promotes colorectal cancer survival and proliferation under glucose restriction via PERK/ATF4/STC2 axis

Tumor competition for nutrients within the microenvironment triggers stress responses to adapt to adverse conditions; however, the mechanism by which a glucose-depleted environment influences tumor fucosylation to promote endoplasmic reticulum (ER) stress remains unclear. In this study, we demonstrate that CRC cells exhibit high expression of FUT3 under glucose-deficient conditions and that FUT3 directly binds to GRP78, inducing its fucosylation. Moreover, we found that fucosylation of GRP78 triggers downstream ER stress signaling pathways and activates the PERK/ATF4/STC2 pathway, leading to enhanced glucose deficiency tolerance in CRC cells. Overall, our study highlights the significant role of FUT3 in the fucosylation of GRP78, which is crucial for the survival and proliferation of CRC cells in a glucose-deficient microenvironment.

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Publication Details

Journal
npj Precision Oncology
Published
2025-12-14
DOI
https://doi.org/10.1038/s41698-025-01216-w
Primary Topic
Endoplasmic Reticulum Stress and Disease
Type
article
Field-Weighted Citation Impact
0.00

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article

FUT3 mediated GRP78 fucosylation promotes colorectal cancer survival and proliferation under glucose restriction via PERK/ATF4/STC2 axis

Yunong Wu, Xinrui Yan, Zelong Han, Kaiwen Qin et al.
npj Precision Oncology
Endoplasmic Reticulum Stress and Disease
article

FUT3 mediated GRP78 fucosylation promotes colorectal cancer survival and proliferation under glucose restriction via PERK/ATF4/STC2 axis

Yunong Wu, Xinrui Yan, Zelong Han, Kaiwen Qin, Y F Luo, Chengcheng He, Changjie Wu, Yulu Shi, Aimin Li, Qingyuan Li, Haonan Zhang, Ruo Wu, Mingsong Li, Xinke Wang, Side Liu, Yu‐Xin Fang
article en

Abstract

Tumor competition for nutrients within the microenvironment triggers stress responses to adapt to adverse conditions; however, the mechanism by which a glucose-depleted environment influences tumor fucosylation to promote endoplasmic reticulum (ER) stress remains unclear. In this study, we demonstrate that CRC cells exhibit high expression of FUT3 under glucose-deficient conditions and that FUT3 directly binds to GRP78, inducing its fucosylation. Moreover, we found that fucosylation of GRP78 triggers downstream ER stress signaling pathways and activates the PERK/ATF4/STC2 pathway, leading to enhanced glucose deficiency tolerance in CRC cells. Overall, our study highlights the significant role of FUT3 in the fucosylation of GRP78, which is crucial for the survival and proliferation of CRC cells in a glucose-deficient microenvironment.

npj Precision OncologyVol. 10(1)
Third Affiliated Hospital of Guangzhou Medical University (CN), Ganzhou People's Hospital (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Nanfang Hospital (CN), Zhuhai People's Hospital (CN), Southern Medical University (CN), Guangzhou Medical University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 58%
Endoplasmic Reticulum Stress and Disease
DOIOpen Access PDFOpenAlex
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