MFGE8 promotes gastric cancer progression by activating the IL-6/JAK/STAT3 signaling

IF 3.7 2区生物学 Q2 CELL BIOLOGY Cellular signalling Pub Date : 2025-01-01 Epub Date: 2024-10-25 DOI:10.1016/j.cellsig.2024.111486

Long-long Ding , Meng Zhang , Tao Zhang , Hui Liu , Peng-fei Liu

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Abstract

Objective

Gastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism.

Methods

GEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments.

Results

MFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth.

Conclusion

MFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.

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MFGE8通过激活IL-6/JAK/STAT3信号传导促进胃癌进展

目的胃癌是全世界发病率和死亡率都很高的恶性肿瘤。含有乳脂球 EGF 和因子 V/VIII 结构域（MFGE8）的蛋白与多种癌症有关。然而，MFGE8在胃癌中的作用仍不明确。方法采用GEPIA分析MFGE8的表达和胃癌患者的生存率。通过免疫组化、PCR和Western blot检测MFGE8在胃癌中的表达。通过一系列细胞功能实验评估了 MFGE8 对胃癌细胞的影响。结果MFGE8在胃癌中过度表达。沉默 MFGE8 可抑制细胞活力、增殖能力、迁移和侵袭能力以及 EMT，但可加速细胞凋亡。而 MFGE8 高表达的胃癌细胞则出现了相反的结果。锌指和含BTB结构域7 A（ZBTB7A）是MFGE8的转录因子。ZBTB7A 的过表达消除了 MFGE8 对胃癌细胞的影响。MFGE8激活了IL-6/JAK/STAT3信号传导。用Stattic（通路抑制剂）抑制IL-6/JAK/STAT3信号转导可以消除MFGE8对IL-6/JAK/STAT3信号转导的促进作用。结论MFGE8通过激活IL-6/JAK/STAT3信号促进胃癌细胞增殖、EMT进展和肿瘤生长。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.