TYRO3 facilitates cell growth and metastasis via activation of the Wnt/β-catenin signaling pathway in human gastric cancer cells
TYRO3 facilitates cell growth and metastasis via activation of the Wnt/β-catenin signaling pathway in human gastric cancer cells
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DOI：
10.18632/aging.102744
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发表时间：
2020-02-15
期刊：
影响因子：
5.2
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Chen, Dehu;Liu, Qinghong;Zhang, Wei
寻找有价值的治疗靶点来改善癌症患者的预后变得越来越重要。尽管越来越多的证据表明TYRO3是各种类型癌症的潜在治疗靶点，但对其在胃癌（GC）发展中的作用知之甚少。本文研究了TYRO3影响GC的功能和分子机制。采用实时荧光定量PCR （qRT-PCR）、western blotting和免疫组织化学检测TYRO3 mRNA和蛋白表达。其他方法包括TYRO3稳定转染GC细胞、伤口愈合、Transwell实验、CCK-8实验、集落形成实验、体外免疫细胞化学和体内肿瘤发生。我们的研究结果表明，高水平的TYRO3与胃癌患者的临床转移和不良预后显著相关。此外，TYRO3沉默在体外和体内均能明显抑制GC细胞的生长、侵袭和转移。相反，TYRO3过表达会导致相反的效果。机制分析显示Wnt/ β -catenin信号通路可能参与tyro3促进的GC细胞行为。总之，我们证明了TYRO3表达的升高通过Wnt/ β -catenin途径促进了胃癌细胞的生长和转移，这提示了一种新的胃癌治疗靶点。
It has become increasingly important to identify valuable therapeutic targets to improve the prognosis of cancer patients. Although emerging evidence has suggested TYRO3 as a potential therapeutic target in various types of cancers, less is known about its role in gastric cancer (GC) development. Herein, we investigated the functional and molecular mechanisms by which TYRO3 influenced GC. TYRO3 mRNA and protein were evaluated by quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry. Other methods including stable transfection of TYRO3 into GC cells, wound healing, Transwell assays, CCK-8 assays, colony formation assays, immunocytochemistry in vitro, and tumorigenesis in vivo were also conducted. Our results indicated that high levels of TYRO3 significantly correlated with clinical metastasis and poor prognoses in patients with GC. In addition, TYRO3 silencing distinctively suppressed GC cell growth, invasion, and metastasis both in vitro and in vivo. Conversely, TYRO3 overexpression led to the opposite effects. Mechanistic analyses revealed that the Wnt/beta-catenin signaling pathway might be involved in TYRO3-facilitated GC cell behavior. Collectively, we demonstrated that elevated TYRO3 expression contributed to GC cell growth and metastasis via the Wnt/beta-catenin pathway, suggesting a novel therapeutic target for GC.