Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion.
Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion.
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DOI：
10.1016/j.devcel.2018.10.026
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发表时间：
2018-11-19
影响因子：
11.8
通讯作者：
Godinho SA
中科院分区：
文献类型：
--
作者：
Arnandis T;Monteiro P;Adams SD;Bridgeman VL;Rajeeve V;Gadaleta E;Marzec J;Chelala C;Malanchi I;Cutillas PR;Godinho SA
中心体异常，特别是中心体扩增，是人类肿瘤的复发特征。体内强迫中心体扩增在肿瘤的发生和发展中起作用。然而，中心体扩增只发生在一部分癌细胞中，因此，部分由于这种异质性，中心体扩增对肿瘤的贡献尚不清楚。本研究表明，在3D乳腺类器官和斑马鱼模型中，多余的中心体通过分泌白介素-8 （IL-8）等蛋白质诱导分泌旁分泌信号轴，从而导致非细胞自主入侵。这种额外的中心体相关分泌表型（ECASP）通过HER2信号激活促进人类乳腺细胞的侵袭。此外，我们证明中心体扩增通过增加nox产生的活性氧（ROS）诱导早期氧化应激反应，进而介导促侵入因子的分泌。具有额外中心体的细胞可以操纵周围细胞的发现突出了这些异常在癌症中意想不到的和深远的后果。中心体扩增诱导非细胞自主侵袭氧化应激导致促侵袭因子IL-8的分泌，IL-8是ROS介导的主要分泌因子，对旁分泌侵袭起重要作用。高ROS可导致具有额外中心体的细胞出现类似衰老的表型。Arnandis等人发现了癌症中中心体扩增的非细胞自主功能。有额外中心体的细胞通过分泌促侵入因子诱导旁分泌侵入。有额外中心体的细胞中活性氧的增加部分调节了分泌的改变。这项工作强调了中心体扩增在癌症中的深远影响。
Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced centrosome amplification in vivo plays a role in tumor initiation and progression. However, centrosome amplification occurs only in a subset of cancer cells, and thus, partly due to this heterogeneity, the contribution of centrosome amplification to tumors is unknown. Here, we show that supernumerary centrosomes induce a paracrine-signaling axis via the secretion of proteins, including interleukin-8 (IL-8), which leads to non-cell-autonomous invasion in 3D mammary organoids and zebrafish models. This extra centrosomes-associated secretory phenotype (ECASP) promotes invasion of human mammary cells via HER2 signaling activation. Further, we demonstrate that centrosome amplification induces an early oxidative stress response via increased NOX-generated reactive oxygen species (ROS), which in turn mediates secretion of pro-invasive factors. The discovery that cells with extra centrosomes can manipulate the surrounding cells highlights unexpected and far-reaching consequences of these abnormalities in cancer. Centrosome amplification induces non-cell-autonomous invasion Oxidative stress leads to the secretion of pro-invasive factors IL-8 is a major ROS-mediated secreted factor important for paracrine invasion High ROS can lead to a senescence-like phenotype in cells with extra centrosomes Arnandis et al. uncovered a non-cell-autonomous function for centrosome amplification in cancer. Cells with extra centrosomes induce paracrine invasion via secretion of pro-invasive factors. Altered secretion is partly regulated by elevated reactive oxygen species in cells with extra centrosomes. This work highlights far-reaching consequences of centrosome amplification in cancer.
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影响因子：
9.2
作者：
Chan JY
通讯作者：
Chan JY
影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
Ewald AJ
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
11.5
作者：
Benoy, IH;Salgado, R;Dirix, LY
通讯作者：
Dirix, LY
DOI：
10.15252/embj.201798576
发表时间：
2018-05-02
期刊：
The EMBO journal
影响因子：
--
作者：
Ganier O;Schnerch D;Oertle P;Lim RY;Plodinec M;Nigg EA
通讯作者：
Nigg EA