Cytoplasmic liver kinase B1 promotes the growth of human lung adenocarcinoma by enhancing autophagy.
Cytoplasmic liver kinase B1 promotes the growth of human lung adenocarcinoma by enhancing autophagy.
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细胞质肝激酶B1通过增强自噬促进人肺腺癌的生长
DOI：
10.1111/cas.13746
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发表时间：
2018-10
期刊：
影响因子：
5.7
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Liu M;Jiang L;Fu X;Wang W;Ma J;Tian T;Nan K;Liang X
肝激酶B1（LKB 1）作为一种肿瘤抑制基因，与包括肺癌在内的多种癌症相关。在本研究中，我们发现LKB 1对肿瘤生长的影响依赖于其在A549和HCC 827细胞中的亚细胞表达。全长LKB 1降低了A549-LKB 1和HCC 827-LKB 1细胞的增殖和克隆形成，但增加了它们的凋亡。在A549-LKB 1 s和HCC 827-LKB 1 S细胞中观察到相反的效果，这些细胞过度表达没有核定位序列的截短LKB 1。截短的胞质LKB 1增强了体内植入肿瘤的生长。在A549和HCC 827细胞中，截短的细胞质LKB 1促进自噬，这不依赖于AMP激活的蛋白激酶和mTOR信号传导。进一步的特征表明，较高水平的胞浆LKB 1表达与190例腺癌患者的晚期TNM分期和总生存率（OS）降低相关。相反，细胞核LKB 1的高表达与早期TNM分期和较长的OS相关。细胞质LKB 1的高表达水平是腺癌患者总生存率低的独立危险因素。总之，我们的研究结果表明，细胞质LKB 1促进肺腺癌的生长，并可能成为肺腺癌的预后标志物。
Liver kinase B1 (LKB1) as a tumor suppression gene that is associated with various kinds of cancers, including lung cancer. In this study, we found that the effect of LKB1 on tumor growth was dependent on its subcellular expression in A549 and HCC827 cells. Full‐length LKB1 decreased the proliferation and clonogenicity of A549‐LKB1 and HCC827‐LKB1 cells, but increased their apoptosis. Opposite effects were observed in A549‐LKB1s and HCC827‐LKB1S cells that overexpressed truncated LKB1 without the nuclear localization sequence. The truncated cytoplasmic LKB1 enhanced the growth of implanted tumors in vivo. The truncated cytoplasmic LKB1 promoted autophagy, which was independent of AMP‐activated protein kinase and mTOR signaling in A549 and HCC827 cells. Further characterization indicated that higher levels of cytoplasmic LKB1 expression were associated with advanced TNM stage and reduced overall survival (OS) in 190 patients with adenocarcinoma. In contrast, high nuclear expression of LKB1 is associated with early TNM stage and longer OS. The high level of cytoplasmic LKB1 expression was an independent risk factor for poor overall survival in patients with adenocarcinoma. Together, our results revealed that cytoplasmic LKB1 promotes the growth of lung adenocarcinoma and could be a prognostic marker for lung adenocarcinoma.
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影响因子：
14.9
作者：
Gupta R;Liu AY;Glazer PM;Wajapeyee N
通讯作者：
Wajapeyee N
影响因子：
2.5
作者：
Lee, W. -S.;Yoo, W. -H.;Chae, H. -J.
通讯作者：
Chae, H. -J.
影响因子：
12.4
作者：
通讯作者：
--
DOI：
10.1126/science.1178377
发表时间：
2009-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zeqiraj E;Filippi BM;Deak M;Alessi DR;van Aalten DM
通讯作者：
van Aalten DM
影响因子：
5.4
作者：
White E
通讯作者：
White E