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.