Leptin secreted by adipocytes promotes EMT transition and endometrial cancer progression via the JAK2/STAT3 signalling pathway

Lifan Shen; Chen Zhang; Kaiying Cui; Xin Liang; Genhai Zhu; Lan Hong

doi:10.1080/21623945.2023.2293273

Leptin secreted by adipocytes promotes EMT transition and endometrial cancer progression via the JAK2/STAT3 signalling pathway

Adipocyte. 2024 Dec;13(1):2293273. doi: 10.1080/21623945.2023.2293273. Epub 2023 Dec 13.

Authors

Lifan Shen¹, Chen Zhang², Kaiying Cui¹, Xin Liang¹, Genhai Zhu¹, Lan Hong¹

Affiliations

¹ Department of Gynecology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
² Department of Central Lab, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.

Abstract

Background: Endometrial cancer is a malignant tumour with a high incidence and mortality rate, and obesity is one of the most significant risk factors for the disease. However, it remains unclear whether leptin affects cell activity, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).

Materials and methods: Samples of endometrial cancer tissue were obtained from clinical patients and nude mice Enzyme-linked immunosorbent assays (ELISAs) were performed to assess leptin levels. Western blotting, immunohistochemical (IHC) and immunofluorescence (IF) analyses were conducted to detect EMT, JAK2/STAT3 signalling pathway proteins, and cell proliferation biomarkers. Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays were used to evaluate cell activity, proliferation, migration, and invasion, respectively.

Results: ELISA, western blot and immunohistochemistry (IHC) analyses showed that leptin was highly expressed, and the JAK2/STAT3 signalling pathway was activated in endometrial cancer patients. Cell-based experiments showed that adipocytes secreted leptin, which increased the levels of leptin, and also promoted cell migration and invasion, EMT transition, and cell activity and proliferation. Leptin accelerated cell progression and promoted EMT via the JAK2/STAT3 signalling pathway in a dose-dependent manner. The tumour-promoting effect of leptin on endometrial cancer cells was further verified by in vivo experiments, in which leptin promoted tumour growth and activated the JAK2/STAT3 signalling pathway.

Conclusion: Leptin secreted by adipocytes promotes EMT transition and endometrial cancer progression via the JAK2/STAT3 signalling pathway in a dose-dependent manner.Highlights Endometrial cancer patients have high levels of leptinLeptin promotes EMT transition via the JAK2/STAT3 signalling pathwayLeptin promotes endometrial cancer progression via the JAK2/STAT3 signalling pathwayLeptin promotes endometrial cancer in a dose-dependent manner.

Keywords: EMT; JAK2/STAT3 signalling pathway; Leptin; cell progression; endometrial cancer.

MeSH terms

Adipocytes / metabolism
Animals
Cell Line, Tumor
Endometrial Neoplasms* / metabolism
Endometrial Neoplasms* / pathology
Epithelial-Mesenchymal Transition
Female
Humans
Janus Kinase 2 / metabolism
Leptin* / metabolism
Mice
Mice, Nude
STAT3 Transcription Factor / metabolism

Substances

JAK2 protein, human
Janus Kinase 2
Leptin
STAT3 protein, human
STAT3 Transcription Factor
LEP protein, human
Lep protein, mouse

Grants and funding

This research is supported by National Natural Science Foundation Cultivation Project-530 Youth Science Fund Project(2021QNXM20) and Hainan Natural Science Foundation Youth Foundation Project (821QN392).