Oncogene-regulated release of extracellular vesicles.
Oncogene-regulated release of extracellular vesicles.
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DOI：
10.1016/j.devcel.2021.05.014
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发表时间：
2021-07-12
影响因子：
11.8
通讯作者：
Goga A
中科院分区：
文献类型：
--
作者：
Kilinc S;Paisner R;Camarda R;Gupta S;Momcilovic O;Kohnz RA;Avsaroglu B;L'Etoile ND;Perera RM;Nomura DK;Goga A
癌基因可以通过改变合成代谢和分解代谢之间的平衡来改变新陈代谢。然而，癌基因如何调控肿瘤细胞生物量仍然知之甚少。利用转化了9个不同癌基因的等基因MCF10A细胞，我们证明了特定的癌基因通过促进EV的释放而减少了癌细胞的生物量。虽然MYC和AURKB诱导的EV数量最多，但每个癌基因都选择性地改变了释放的EV的蛋白质组成。同样，癌基因会改变分泌的miRNAs。MYC过表达细胞需要神经酰胺，而AURKB需要ESCRT来释放高水平的EV。我们发现MYC上调与激活RAS/MEK/ERK信号通路调节某些肿瘤细胞中EV的释放之间存在反向关系。最后，在MYC和AURKB的背景下，溶酶体基因和活性被下调，这表明细胞内容物不是被降解，而是通过EVS释放。因此，癌基因通过EV差异释放介导的生物量调节是一种新的代谢表型。Kilincet.艾尔证明癌基因改变了释放的囊泡数量和大小以及它们的异质性。癌基因改变了参与SEV产生的神经酰胺和ESCRT途径。MYC和AURKB癌基因下调溶酶体途径，并利用EV释放来维持细胞内环境的稳定。
Oncogenes can alter metabolism by changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic MCF10A cells transformed with nine different oncogenes, we show that specific oncogenes reduce the biomass of cancer cells by promoting EV release. While MYC and AURKB elicited the highest number of EVs, each oncogene selectively altered the protein composition of released EVs. Likewise, oncogenes alter secreted miRNAs. MYC overexpressing cells require ceramide, while AURKB require ESCRT to release high levels of EVs. We identify an inverse relationship between MYC upregulation and activation of the RAS/MEK/ERK signaling pathway for regulating EV release in some tumor cells. Finally, lysosome genes and activity are downregulated in the context of MYC and AURKB, suggesting that cellular contents instead of being degraded, were released via EVs. Thus, oncogene mediated biomass regulation via differential EV release is a new metabolic phenotype. Kilinc et. al. demonstrate that oncogenes alter released vesicle number and size as well as their heterogeneity. Oncogenes alter ceramide and ESCRT pathways involved in sEV production. MYC and AURKB oncogenes downregulate lysosome pathway and utilize EV release to maintain cellular homeostasis.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
影响因子：
11.2
作者：
Cao Z;Fan-Minogue H;Bellovin DI;Yevtodiyenko A;Arzeno J;Yang Q;Gambhir SS;Felsher DW
通讯作者：
Felsher DW
影响因子：
82.9
作者：
Goga, Andrei;Yang, Dun;Bishop, J. Michael
通讯作者：
Bishop, J. Michael
影响因子：
4
作者：
Colombo, Marina;Moita, Catarina;Raposo, Graca
通讯作者：
Raposo, Graca