Leptin stimulates migration and invasion and maintains cancer stem‑like properties in gastric cancer cells

Park,Ki Bum; Kim,Eun Young; Chin,Hyungmin; Yoon,Dong Joon; Jun,Kyong-Hwa

doi:10.3892/or.2022.8377

Leptin stimulates migration and invasion and maintains cancer stem‑like properties in gastric cancer cells

Authors:
- Ki Bum Park
- Eun Young Kim
- Hyungmin Chin
- Dong Joon Yoon
- Kyong-Hwa Jun
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Affiliations: Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Paldal‑gu, Suwon‑si, Gyeonggi‑do 16247, Republic of Korea, Department of Surgery, Uijeongbu St. Mary Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu‑si, Gyeonggi‑do 11765, Republic of Korea, Clinical Medical Laboratory, St. Vincent's Hospital, Paldal‑gu, Suwon‑si, Gyeonggi‑do 16247, Republic of Korea
Published online on: July 21, 2022 https://doi.org/10.3892/or.2022.8377
Article Number: 162
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Obesity is a risk factor for various types of cancer. Leptin, an adipocyte‑derived hormone, may stimulate the proliferation of gastric cancer cells. However, the effect of leptin and underlying mechanism in gastric cancer remain unclear. In the present study, the role of leptin in gastric cancer was evaluated. The effect of leptin on the JAK‑STAT and MEK signaling pathways was investigated in gastric cancer cells using wound‑healing and cell invasion assays, immunoblotting and inhibition studies. Cancer‑initiating cells derived from gastric cancer cells were used to investigate the effect of leptin on the maintenance of stemness and epithelial‑mesenchymal transition (EMT) by immunoblotting. Clinicopathological characteristics including the serum leptin level and overall survival (OS) were analyzed in patients with (n=23) and without (n=23) obesity. Leptin induced the migration and invasion of gastric cancer cells by activating AKT and ERK and upregulating vascular endothelial growth factor (VEGF). Leptin increased the mRNA and protein levels of markers of stemness (CD44) and the EMT (Snail and N‑cadherin). Pharmacological inhibitors of the JAK‑STAT and MEK signaling pathways decreased leptin‑induced migration and invasion, and the expression of VEGF. Obesity was associated with an elevated leptin level and body mass index was positively correlated with the leptin level (P=0.001 for both). The 5‑year OS rate was not significantly different between the two groups (P=0.098). Leptin stimulates the migration and invasion of gastric cancer cells by activating the JAK‑STAT and MEK pathways, and contributes to the maintenance of cancer stemness and metastatic potential. The present findings support an adverse effect of obesity in gastric cancer. Consequently, targeting of leptin‑associated signaling pathways may have therapeutic potential for gastric cancer.

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