College of Basic Medical Science, Dalian Medical University, Dalian, China.
Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Cell Death Dis. 2021 Nov 20;12(12):1094. doi: 10.1038/s41419-021-04388-y.
Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance of Lactobacillus, especially L. iners, was significantly reduced. Meanwhile, the abundance of L.iners was positively correlated with core fucosylation levels. The L. iners metabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.
阴道微生态失调常发生于宫颈癌患者中。黏膜上皮细胞的岩藻糖化与其微生物定植密切相关,并在保护阴道黏膜上皮细胞中发挥重要作用。然而,关于阴道微生态失调与异常黏膜上皮细胞岩藻糖化之间的关系及其在宫颈癌发生发展中的作用尚无报道。本研究报道宫颈癌患者的血清、脱落宫颈细胞和肿瘤组织中核心岩藻糖基化水平显著降低。核心岩藻糖基转移酶基因(Fut8)敲除促进了宫颈癌细胞的增殖和迁移。在宫颈癌患者中,阴道微生态失调以及乳杆菌,尤其是 L. iners 的丰度显著降低。同时,L. iners 的丰度与核心岩藻糖基化水平呈正相关。L. iners 的代谢产物乳酸可通过乳酸-Gpr81 复合物激活 Wnt 通路,增加表皮细胞中的核心岩藻糖基化水平,抑制宫颈癌细胞的增殖和迁移,在调节阴道微生态和预防宫颈癌方面具有应用前景。