SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.
SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.
复制标题
SUN2通过抑制肺癌中的Warburg效应发挥抑癌功能
DOI：
10.1038/srep17940
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发表时间：
2015-12-10
影响因子：
4.6
通讯作者：
Sang Y
中科院分区：
文献类型：
--
作者：
Lv XB;Liu L;Cheng C;Yu B;Xiong L;Hu K;Tang J;Zeng L;Sang Y
SUN 2是位于内核膜的LINC（核骨架和细胞骨架连接体）复合物的关键成分，在肺癌中发挥着未知的作用。我们发现，与配对的正常组织相比，肺癌组织中的SUN 2表达降低，并且较高的SUN 2水平预测较好的总生存率和首次进展生存率。SUN 2的过表达抑制肺癌细胞的增殖、集落形成和迁移，而SUN 2的敲低促进细胞增殖和迁移。此外，SUN 2通过诱导细胞凋亡增加肺癌对顺铂的敏感性。从机制上讲，我们发现SUN 2通过降低GLUT 1和LDHA的表达来抑制瓦尔堡效应，从而发挥其肿瘤抑制功能。研究结果表明，SUN 2通过抑制瓦尔堡效应在肺癌的发生发展中起重要作用，SIRT 5/SUN 2轴可能为肺癌的治疗提供新的思路。
SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell proliferation and migration. Additionally, SUN2 increases the sensitivity of lung cancer to cisplatin by inducing cell apoptosis. Mechanistically, we showed that SUN2 exerts its tumor suppressor functions by decreasing the expression of GLUT1 and LDHA to inhibit the Warburg effect. Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2.Taken together, our findings indicate that SUN2 is a key component in lung cancer progression by inhibiting the Warburg effect and that the novel SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer.