LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells.
LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells.
复制标题
LASS2 通过 ERK/Drp1 调节膀胱癌细胞的线粒体动力学调节侵袭和化疗耐药
DOI：
10.7150/jca.23087
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Huang L;Luan T;Chen Y;Bao X;Huang Y;Fu S;Wang H;Wang J
线粒体协调了许多重要的细胞能量产生和分配过程。线粒体功能的改变与癌症进展有关。本研究旨在探讨线粒体动力学在LASS2诱导的膀胱癌细胞侵袭和化疗耐药中的作用。用J82和BIU87细胞株转染LASS2质粒，5637细胞株敲低siRNA。Matrigel侵袭实验和Annexin V/PI染色显示LASS2负向调控癌细胞侵袭和化疗耐药。JC-1染色提示LASS2过表达下调线粒体膜电位。Mitotracker染色显示LASS2诱导线粒体融合，抑制线粒体裂变。此外，LASS2过表达下调线粒体裂变蛋白p-Drp1、Drp1和Fis1的表达。而LASS2的耗竭则表现出相反的效果。Drp1抑制剂Mdivi可消除LASS2 siRNA诱导的侵袭和化学耐药。此外，我们发现LASS2过表达可以抑制ERK的磷酸化，而ERK作用于Drp1的上游。ERK抑制剂PD98059抑制Drp1磷酸化，消除LASS2缺失的影响。综上所述，本研究表明LASS2通过调控ERK-Drp1诱导的线粒体动力学抑制膀胱癌侵袭和化疗耐药。
Mitochondria coordinated a lot of vital cellular processes of energy production and distribution. Change of mitochondrial functions has been implicated in cancer progression. The present study aims to investigate the involvement of mitochondria dynamics in LASS2 induced invasion and chemoresistance of bladder cancer cells. J82 and BIU87 cell lines were used for LASS2 plasmid transfection while siRNA knockdown was carried out in 5637 cell line. Matrigel invasion assay and Annexin V/PI staining demonstrated that LASS2 negatively regulated cancer cell invasion and chemoresistance. JC-1 staining suggested that LASS2 overexpression downregulated mitochondrial membrane potential. Mitotracker staining showed that LASS2 induced mitochondrial fusion and inhibited mitochondrial fission. In addition, LASS2 overexpression downregulated expression of mitochondrial fission protein p-Drp1 Drp1 and Fis1. While depletion of LASS2 exhibited the opposite effects. Drp1 inhibitor Mdivi abolished invasion and chemoresistance induced by LASS2 siRNA. Furthermore, we found that LASS2 overexpression could inhibit phosphorylation of ERK, which act upstream of Drp1. ERK inhibitor PD98059 suppressed Drp1 phosphorylation and abrogated the effects of LASS2 depletion. In conclusion, the present study demonstrated that LASS2 inhibits bladder cancer invasion and chemoresistance through regulation of ERK-Drp1 induced mitochondrial dynamics.
登录
查看更多内容
AGPAT9 通过 KLF4/LASS2/V-ATPase 信号通路抵消乳腺癌中的酸性肿瘤微环境，从而抑制细胞生长、侵袭和转移。
影响因子：
--
作者：
Fan SH;Wang YY;Wu ZY;Zhang ZF;Lu J;Li MQ;Shan Q;Wu DM;Sun CH;Hu B;Zheng YL
通讯作者：
Zheng YL
LASS2通过调节ATP酶活性抑制膀胱癌的生长和侵袭
影响因子：
2.9
作者：
Wang H;Zuo Y;Ding M;Ke C;Yan R;Zhan H;Liu J;Wang W;Li N;Wang J
通讯作者：
Wang J
影响因子：
3.4
作者：
Wang, Haifeng;Wang, Jiansong;Ke, Changxin
通讯作者：
Ke, Changxin
DOI：
10.1073/pnas.1505411112
发表时间：
2015-07-21
影响因子：
11.1
作者：
Baker, Nicola;Hamilton, Graham;Horn, David
通讯作者：
Horn, David
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin