Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Institute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Commun Biol. 2024 Oct 10;7(1):1297. doi: 10.1038/s42003-024-06993-x.
Colorectal cancer (CRC) ranks as the second most lethal cancer worldwide because of its high rate of metastasis, and approximately 20% of CRC patients have metastases at initial diagnosis. Metabolic reprogramming, a hallmark of cancer cells, has been implicated in the process of metastasis. We previously demonstrated that fucosyltransferase 2 (FUT2) promotes the malignancy of CRC cells, however, the underlying mechanisms remain unclear. Here, bioinformatic analysis revealed that FUT2 is associated with the malignant phenotype and fatty acid metabolism in CRC. FUT2 knockdown decreased glucose uptake and de novo fatty acid synthesis, which in turn inhibited the proliferation and metastasis of CRC cells. Mechanistically, FUT2 promotes YAP1 nuclear translocation and stabilizes mSREBP-1 by fucosylation, thus promoting de novo fatty acid synthesis in CRC cells. In summary, this study demonstrates that FUT2 promotes the proliferation and metastasis of CRC cells by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1, indicating that FUT2 might be a potential target for developing therapeutic strategies against CRC.
结直肠癌（CRC）因其高转移率而成为全球第二大最致命的癌症，约 20%的 CRC 患者在初始诊断时就已经发生转移。代谢重编程是癌细胞的一个标志，与转移过程有关。我们之前的研究表明，岩藻糖基转移酶 2（FUT2）促进 CRC 细胞的恶性表型，然而，其潜在机制尚不清楚。在这里，生物信息学分析表明 FUT2 与 CRC 中的恶性表型和脂肪酸代谢有关。FUT2 的敲低降低了葡萄糖摄取和从头脂肪酸合成，进而抑制了 CRC 细胞的增殖和转移。在机制上，FUT2 通过岩藻糖基化促进 YAP1 的核易位和 mSREBP-1 的稳定，从而促进 CRC 细胞中的从头脂肪酸合成。综上所述，这项研究表明，FUT2 通过 YAP/TAZ 信号和 SREBP-1 重编程脂肪酸代谢促进 CRC 细胞的增殖和转移，表明 FUT2 可能是开发针对 CRC 的治疗策略的潜在靶点。
