Mitochondrial dynamics regulates migration and invasion of breast cancer cells

MFN1型 生物 线粒体分裂 线粒体 板层 基因沉默 线粒体融合 细胞生物学 癌症研究 癌细胞 DNM1L型 转移 癌症 细胞迁移 细胞 线粒体DNA 生物化学 遗传学 基因
作者
Jing Zhao,Jinhua Zhang,Meifang Yu,Yan Xie,Yen‐Tsung Huang,Dennis W. Wolff,Peter W. Abel,Yuhai Tu
出处
期刊:Oncogene [Springer Nature]
卷期号:32 (40): 4814-4824 被引量:658
标识
DOI:10.1038/onc.2012.494
摘要

Mitochondria are highly dynamic and undergo constant fusion and fission that are essential for maintaining physiological functions of cells. Although dysfunction of mitochondria has been implicated in tumorigenesis, little is known about the roles of mitochondrial dynamics in metastasis, the major cause of cancer death. In the present study, we found a marked upregulation of mitochondrial fission protein dynamin-related protein 1 (Drp1) expression in human invasive breast carcinoma and metastases to lymph nodes. Compared with non-metastatic breast cancer cells, mitochondria also were more fragmented in metastatic breast cancer cells that express higher levels of total and active Drp1 and less mitochondrial fusion protein 1 (Mfn1). Silencing Drp1 or overexpression of Mfn1 resulted in mitochondria elongation or clusters, respectively, and significantly suppressed metastatic abilities of breast cancer cells. In contrast, silencing Mfn proteins led to mitochondrial fragmentation and enhanced metastatic abilities of breast cancer cells. Interestingly, these manipulations of mitochondrial dynamics altered the subcellular distribution of mitochondria in breast cancer cells. For example, silencing Drp1 or overexpression of Mfn1 inhibited lamellipodia formation, a key step for cancer metastasis, and suppressed chemoattractant-induced recruitment of mitochondria to lamellipodial regions. Conversely, silencing Mfn proteins resulted in more cell spreading and lamellipodia formation, causing accumulation of more mitochondria in lamellipodia regions. More importantly, treatment with a mitochondrial uncoupling agent or adenosine triphosphate synthesis inhibitor reduced lamellipodia formation and decreased breast cancer cell migration and invasion, suggesting a functional importance of mitochondria in breast cancer metastasis. Together, our findings show a new role and mechanism for regulation of cancer cell migration and invasion by mitochondrial dynamics. Thus targeting dysregulated Drp1-dependent mitochondrial fission may provide a novel strategy for suppressing breast cancer metastasis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
菜籽完成签到,获得积分10
刚刚
刚刚
大模型应助加油采纳,获得10
1秒前
zyf完成签到,获得积分10
2秒前
沉默芸发布了新的文献求助10
3秒前
科研通AI5应助菜籽采纳,获得10
4秒前
4秒前
稳赚赚完成签到,获得积分10
4秒前
5秒前
6秒前
Akim应助汤飞柏采纳,获得10
6秒前
可靠豌豆发布了新的文献求助10
7秒前
大个应助爱听歌笑寒采纳,获得10
7秒前
8秒前
9秒前
orixero应助刀客特幽采纳,获得10
11秒前
加油发布了新的文献求助10
12秒前
SpONGeBOb完成签到 ,获得积分10
12秒前
12秒前
wilson完成签到,获得积分10
12秒前
ZUOWEI发布了新的文献求助10
12秒前
兮兮兮发布了新的文献求助10
12秒前
传奇3应助薄红采纳,获得10
13秒前
华仔应助天空没有极限采纳,获得10
14秒前
阔达斑马应助神勇乐安采纳,获得30
14秒前
16秒前
16秒前
个性的紫菜应助DAN_采纳,获得10
16秒前
汤飞柏发布了新的文献求助10
19秒前
wanci应助liquor采纳,获得10
20秒前
武似星飞完成签到,获得积分10
20秒前
kytsg完成签到 ,获得积分10
24秒前
26秒前
彩色菲鹰完成签到,获得积分10
27秒前
29秒前
qiao应助小林采纳,获得10
29秒前
科研通AI5应助DAN_采纳,获得10
29秒前
清澄完成签到,获得积分10
31秒前
bkagyin应助123采纳,获得10
33秒前
35秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Technologies supporting mass customization of apparel: A pilot project 450
Mixing the elements of mass customisation 360
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
the MD Anderson Surgical Oncology Manual, Seventh Edition 300
Nucleophilic substitution in azasydnone-modified dinitroanisoles 300
Political Ideologies Their Origins and Impact 13th Edition 260
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3781625
求助须知:如何正确求助?哪些是违规求助? 3327197
关于积分的说明 10230039
捐赠科研通 3042069
什么是DOI,文献DOI怎么找? 1669783
邀请新用户注册赠送积分活动 799315
科研通“疑难数据库(出版商)”最低求助积分说明 758774