4.7 Article

Lactobacillus spp. create a protective micro-ecological environment through regulating the core fucosylation of vaginal epithelial cells against cervical cancer

Journal

CELL DEATH & DISEASE
Volume 12, Issue 12, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41419-021-04388-y

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Funding

  1. National Natural Science Foundation of China [31870797, 31900920]
  2. Nutrition and Care of Maternal & Child Research Fund Project of Guangzhou Biostime Institute of Nutrition Care [2019BINCMCF02, 2018BINCMCF39]
  3. Dalian Medical Science Research Project [1912038]
  4. Dalian Science and Technology Innovation Project [2020JJ27SN068]
  5. Liaoning Provincial Program for Top Discipline of Basic Medical Sciences, China

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Vaginal dysbiosis is related to the development of cervical cancer, and the abundance of L. iners is positively correlated with core fucosylation levels. Lactate can inhibit the proliferation and migration of cervical cancer cells by activating the Wnt pathway, showing potential in regulating vaginal microecology and preventing cervical cancer.
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.

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