Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells.
Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells.
复制标题
Klotho 过表达抑制 HELF 成纤维细胞 SASP 相关的对非小细胞肺癌细胞的促肿瘤作用
DOI：
10.7150/jca.23967
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Chen B;Liang Y;Chen L;Wei Y;Li Y;Zhao W;Wu J
肺癌（Lung cancer，LC）是世界范围内最常见的癌症死亡原因，也是一种与年龄密切相关的疾病。Klotho是一种新的抗衰老基因，已被证明在调节衰老和包括LC在内的年龄相关疾病的发展中起着关键作用。然而，Klotho是否是衰老和LC之间的关键环节仍然是未知的。在这里，我们报告Klotho可以通过调节衰老相关分泌表型（SASP）间接抑制LC的生长和发育。我们发现衰老的肺成纤维细胞（SLF）可以促进IL-6和IL-8的产生，这可以通过过表达Klotho来有效地抑制。用SLF衍生的条件培养基（CM）培养LC细胞，其存活率和迁移率明显增加，p-STAT 3和α-SMA表达明显增加，P53和E-cadherin表达明显降低。然而，使用来源于过表达Klotho的SLF的CM培养LC细胞，所有上述结果几乎完全逆转。这些结果表明Klotho可以调节SLF细胞外IL-6和IL-8的释放，从而影响LC细胞的STAT 3活化、P53表达和上皮-间质转化（EMT），最终间接抑制LC细胞的生长和迁移。
Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a key link between aging and LC is still unknown. Here we report that Klotho can indirectly inhibit LC growth and development through regulating senescence-associated secretory phenotype (SASP). We found that senescent lung fibroblasts (SLF) can promote production of IL-6 and IL-8, which can be effectively inhibited by overexpressing Klotho. Using conditioned medium (CM) derived from SLF to culture LC cells, the LC cells show obvious increase of viability and migration rates, significant increase expression of p-STAT3 and α-SMA, and decrease expression of P53 and E-cadherin. However, using CM derived from SLF overexpressed Klotho to culture LC cells, all above results are nearly completely reversed. Thus, these results suggest that Klotho can regulate SLF extracellular release of IL-6 and IL-8, which can influence STAT3 activation, P53 expression and epithelial-mesenchymal transition (EMT) of LC cells, finally inhibiting LC cells growth and migration indirectly.
登录
查看更多内容
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J
DOI：
10.1083/jcb.201009094
发表时间：
2011-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rodier F;Campisi J
通讯作者：
Campisi J
影响因子：
--
作者：
Lugo R;Gabasa M;Andriani F;Puig M;Facchinetti F;Ramírez J;Gómez-Caro A;Pastorino U;Fuster G;Almendros I;Gascón P;Davalos A;Reguart N;Roz L;Alcaraz J
通讯作者：
Alcaraz J
Klotho 抑制人肺癌细胞系 A549 生长并促进细胞凋亡
DOI：
10.1186/1756-9966-29-99
发表时间：
2010-07-19
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chen B;Wang X;Zhao W;Wu J
通讯作者：
Wu J