Department of General Surgery, Taizhou People's Hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou 225300, China.
Department of Infectious Diseases, Taizhou People's Hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou 225300, China.
Aging (Albany NY). 2020 Feb 4;12(3):2261-2274. doi: 10.18632/aging.102744.
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 and tumorigenesis 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 and . Conversely, TYRO3 overexpression led to the opposite effects. Mechanistic analyses revealed that the Wnt/β-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/β-catenin pathway, suggesting a novel therapeutic target for GC.
确定有价值的治疗靶点以改善癌症患者的预后变得越来越重要。尽管有新的证据表明 TYRO3 是各种类型癌症的潜在治疗靶点，但关于其在胃癌 (GC) 发展中的作用知之甚少。在此，我们研究了 TYRO3 影响 GC 的功能和分子机制。通过定量实时 PCR (qRT-PCR)、western blot 和免疫组织化学评估 TYRO3 mRNA 和蛋白质。还进行了其他方法，包括将 TYRO3 稳定转染到 GC 细胞中、划痕愈合、Transwell 测定、CCK-8 测定、集落形成测定、免疫细胞化学和肿瘤发生。我们的结果表明，TYRO3 的高水平与 GC 患者的临床转移和预后不良显著相关。此外，TYRO3 沉默明显抑制 GC 细胞的生长、侵袭和转移。相反，TYRO3 的过表达导致相反的效果。机制分析表明，Wnt/β-catenin 信号通路可能参与 TYRO3 促进的 GC 细胞行为。总之，我们证明升高的 TYRO3 表达通过 Wnt/β-catenin 通路促进 GC 细胞的生长和转移，提示 GC 的一个新的治疗靶点。
