Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR–Hippo–YAP pathway

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  • Shi‐Bo Bian
    Department of General Surgery Beijing Friendship Hospital, Capital Medical University Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases Beijing China
  • Yun Yang
    Department of General Surgery Beijing Friendship Hospital, Capital Medical University Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases Beijing China
  • Wen‐Quan Liang
    Department of General Surgery Chinese People's Liberation Army General Hospital Beijing China
  • Ke‐Cheng Zhang
    Department of General Surgery Chinese People's Liberation Army General Hospital Beijing China
  • Lin Chen
    Department of General Surgery Chinese People's Liberation Army General Hospital Beijing China
  • Zhong‐Tao Zhang
    Department of General Surgery Beijing Friendship Hospital, Capital Medical University Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases Beijing China

書誌事項

公開日
2020-08-22
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1111/nyas.14466
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>The long‐term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR–Hippo–YAP signaling. LIF may therefore be a useful biomarker for GC.</jats:p>

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