Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR–Hippo–YAP pathway,Annals of the New York Academy of Sciences

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Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR–Hippo–YAP pathway
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2020-08-22 , DOI: 10.1111/nyas.14466
Shi-Bo Bian _{1,

2} , Yun Yang ₁ , Wen-Quan Liang ₂ , Ke-Cheng Zhang ₂ , Lin Chen ₂ , Zhong-Tao Zhang ₁

Affiliation

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.

中文翻译：

白血病抑制因子通过LIFR-Hippo-YAP通路促进胃癌细胞增殖、迁移和侵袭

尽管最近有一些改善，但胃癌 (GC) 患者的长期结果仍然不令人满意。白血病抑制因子 (LIF) 是一些实体瘤的预后生物标志物，但其在 GC 中的作用仍然未知。在这项研究中，我们证明了 LIF 和 LIF 受体 (LIFR) 在 GC 组织中过度表达，并确定它们之间存在相关性。LIF 和 LIFR 表达与肿瘤分化、淋巴血管浸润、肿瘤分期、淋巴结转移和 pTNM 分期有关，表明它们可能是有用的预后因素。LIF促进GC细胞增殖、集落形成、侵袭、迁移和肿瘤生长；它还促进细胞周期进程并抑制细胞凋亡；敲除 LIFR 基因逆转了 LIF 的影响。LIF 抑制了 Hippo 通路的活性，导致 YAP 磷酸化减少、YAP 核易位增加和细胞增殖增加。最后，沉默 YAP mRNA 表达抑制细胞增殖。总体而言，结果表明 LIF 通过 LIFR-Hippo-YAP 信号传导促进 GC 细胞的恶性生物学行为。因此，LIF 可能是 GC 的有用生物标志物。

更新日期：2020-08-22

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