Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Neoplasma. 2019 May 23;66(3):367-376. doi: 10.4149/neo_2018_180820N630. Epub 2018 Dec 12.
Liver kinase B1 (LKB1) is revealed to have a close relationship with cancers. However, the underlying mechanism remains unclear. This study aimed to reveal the mechanism through which LKB1 performed its role in lung cancer. LKB1 shRNA and overexpression plasmid were employed to investigate the role of LKB1 in lung cancer in vitro and in vivo. The involvement of Shh signaling pathway was assessed by western blot. Silence of LKB1 promoted, while overexpression of LKB1 inhibited the migration, invasion and angiogenesis of lung cancer cells. Further study showed that Shh signaling pathway was suppressed by LKB1. Cyclopamine, a Shh signaling pathway inhibitor, reduced the effects of LKB1 silence, indicating that LKB1 inhibits the migration, invasion and angiogenesis through suppressing the Shh signaling pathway. In vivo study also showed that Shh signaling pathway was involved in the modulation of LKB1 on the metastasis and angiogenesis of lung cancer. Our study demonstrates that LKB1 inhibits the metastasis and angiogenesis of lung cancer through suppressing the Shh signaling pathway.
肝激酶 B1（LKB1）与癌症密切相关。然而，其潜在机制尚不清楚。本研究旨在揭示 LKB1 在肺癌中发挥作用的机制。通过 LKB1 shRNA 和过表达质粒研究 LKB1 在体外和体内对肺癌的作用。通过 Western blot 评估 Shh 信号通路的参与。沉默 LKB1 促进，而 LKB1 的过表达抑制肺癌细胞的迁移、侵袭和血管生成。进一步的研究表明 LKB1 抑制了 Shh 信号通路。Shh 信号通路抑制剂环巴胺降低了 LKB1 沉默的作用，表明 LKB1 通过抑制 Shh 信号通路抑制迁移、侵袭和血管生成。体内研究也表明 Shh 信号通路参与了 LKB1 对肺癌转移和血管生成的调节。我们的研究表明，LKB1 通过抑制 Shh 信号通路抑制肺癌的转移和血管生成。
