Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.
Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.
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SIRT2介导的细胞外蛋白脱乙酰化促进肺癌转移
DOI：
10.1002/advs.202205462
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发表时间：
2023-01
期刊：
影响因子：
15.1
通讯作者：
Chinn, Y. Eugene
中科院分区：
文献类型：
--
作者：
Wu, Meng;Zhang, Jian-Bin;Xiong, Yi-Wei;Zhao, Yong-Xu;Zheng, Meng-Ge;Huang, Xia-Li;Huang, Fang;Wu, Xing-Xing;Li, Xue;Fan, Wei-Jiao;Hu, Lin;Zeng, Yuan-Yuan;Cheng, Xia-Ju;Yue, Ji-Cheng;Du, Juan-Juan;Chen, Nan-Nan;Wei, Wen-Xiang;Yao, Qing-Hua;Lu, Xiao-mei;Huang, Chao;Deng, Jiong;Chang, Zhi-Jie;Liu, He-Bin;Zhao, Ting C.;Chinn, Y. Eugene
在许多独立的研究中观察到了胞外蛋白质的乙酰化，其中特别关注翻译后微环境蛋白质修饰的动态变化。虽然细胞外蛋白在微环境分布之前可以在细胞内被乙酰化，但它们在肿瘤微环境中的去乙酰化仍然是难以捉摸的。本文描述了多种乙酰基VWA结构域蛋白，包括整合素β3(ITGB3)和6A胶原蛋白(COL6A)在细胞外空间被Sirtuin家族成员SIRT2去乙酰化。巨噬细胞在Toll样受体(TLR)家族成员TLR4或TLR2激活后分泌SIRT2。TLR激活的SIRT2经历自噬小体易位。肿瘤坏死因子受体相关因子6(TRAF6)介导的自噬通量响应TLR2/4的激活，然后将SIRT2泵入微环境，发挥细胞外SIRT2(ESIRT2)的作用。在细胞外空间，eSIRT2去乙酰化aK416上的ITGB3，参与细胞的附着和迁移，从而促进癌细胞的转移。在肺癌患者中，血清eSIRT2水平显著升高与癌细胞ITGB3-K416乙酰化水平显著降低相关。因此，胞外空间是一个亚细胞样细胞器的竞技场，eSIRT2通过催化胞外蛋白去乙酰化促进癌细胞转移。SIRT2受刺激后从巨噬细胞分泌到微环境中。SIRT2在自噬体内被检测到，自噬器官作为SIRT2跨质膜运输的管道。有趣的是，SIRT2可能通过去乙酰化包括ITGB3和胶原蛋白在内的多种细胞外蛋白来促进癌细胞的转移。它通过靶向微环境中的SIRT2，为阻断肿瘤转移提供了新的手段。
Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post‐translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro‐environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl‐vWA domain‐carrying proteins including integrin β3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll‐like receptor (TLR) family member TLR4 or TLR2 activation. TLR‐activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)‐mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3‐K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle‐like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation. SIRT2 is secreted into the microenvironment from macrophages upon stimulation. SIRT2 is detected within the autophagosome and the autophagic apparatus serves as conduits for the transport of SIRT2 across plasma membrane. Intriguingly, SIRT2 promotes cancer cell metastasis presumably via deacetylating multiple extracellular proteins including ITGB3 and collagens. It provide new means by targeting SIRT2 in the microenvironment in order to block metastasis.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
7.3
作者：
Iula L;Keitelman IA;Sabbione F;Fuentes F;Guzman M;Galletti JG;Gerber PP;Ostrowski M;Geffner JR;Jancic CC;Trevani AS
通讯作者：
Trevani AS
影响因子：
8.8
作者：
Berry, Kayla N.;Brett, Tom J.
通讯作者：
Brett, Tom J.
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
3.7
作者：
Grbesa I;Pajares MJ;Martínez-Terroba E;Agorreta J;Mikecin AM;Larráyoz M;Idoate MA;Gall-Troselj K;Pio R;Montuenga LM
通讯作者：
Montuenga LM