1. Academic Validation
  2. β-Klotho inhibits CSF-1 secretion and delays the development of endometrial cancer

β-Klotho inhibits CSF-1 secretion and delays the development of endometrial cancer

  • Cell Cycle. 2022 Oct;21(20):2132-2144. doi: 10.1080/15384101.2022.2092180.
Fu Hua 1 Xiaogang Chen 2
Affiliations

Affiliations

  • 1 Department of Gynecology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
  • 2 Department of Orthopedics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Abstract

Senescent cells can drive tumors development by promoting chronic inflammation. There is a significant correlation between β-Klotho expression profiles and endometrial Cancer (EC). However, how β-Klotho regulates the occurrence and development of uterine EC remains to be further studied. Our research found that compared with normal endometrial tissues, β-Klotho expression levels in EC tissues were significantly reduced; overexpression of β-Klotho significantly inhibited aging, proliferation and migration but promoted Apoptosis of EC cells cultured in vitro. In normal endometrial cells, results confirmed that reduced levels of β-Klotho promoted CSF-1 secretion, and the migration ability of macrophages was significantly enhanced when co-cultured with normal endometrial cells. In contrast, the expression of CSF-1 was significantly reduced after overexpression of β-Klotho in EC cells, and the macrophage migration ability is significantly weakened when co-cultured with EC cells. Therefore, we believe that β-Klotho influences macrophage migration by regulating the expression of CSF-1, thereby interfering with the progression of EC. We investigated in depth the mechanism of β-Klotho regulating CSF-1 secretion and found that β-Klotho inhibits the phosphorylation of p65, which blocked the nuclear translocation of p65, thereby inhibiting the secretion of CSF-1 by EC cells. The above results indicate that β-Klotho-mediated inhibition of CSF-1 secretion reduces the migration of macrophages to tumor tissue and delays the progression of EC.

Keywords

CSF-1; endometrial cancer cells; macrophages; p65; Β-Klotho.

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