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

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 leptin

• Leptin promotes EMT transition via the JAK2/STAT3 signalling pathway

• Leptin promotes endometrial cancer progression via the JAK2/STAT3 signalling pathway

• Leptin promotes endometrial cancer in a dose-dependent manner

KEYWORDS:

• Leptin
• endometrial cancer
• EMT
• cell progression
• JAK2/STAT3 signalling pathway

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contributions

(I) Study design/planning: Lifan Shen; (II) Data collection/entry: Lifan Shen, Chen Zhang, Xin Liang, Kaiying Cui; (III) Data analysis/statistics: Lifan Shen, Chen Zhang; (IV) Data interpretation: Lifan Shen, Chen Zhang, Genhai Zhu, Lan Hong; (V) Preparation of manuscript: Lifan Shen; (VI) Literature analysis/search: All authors; (VII) Funding acquisition: National Natural Science Foundation Cultivation Project-530 Youth Science Fund Project(2021QNXM20); (VIII) Final approval of manuscript: All authors.

Ethics statement

All the study participants signed an informed consent for the inclusion in the study. The study was approved by Ethical Committee of Hainan General Hospital (No. 2022–597)

Data availability statement

All data are available from the figshare with request. (doi: 10.6084/m9.figshare.23742015)

Additional information

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).