SIRT7 inactivation reverses metastatic phenotypes in epithelial and mesenchymal tumors.
SIRT7 inactivation reverses metastatic phenotypes in epithelial and mesenchymal tumors.
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DOI：
10.1038/srep09841
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发表时间：
2015-04-29
影响因子：
4.6
通讯作者：
Chua KF
中科院分区：
文献类型：
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作者：
Malik S;Villanova L;Tanaka S;Aonuma M;Roy N;Berber E;Pollack JR;Michishita-Kioi E;Chua KF
90%以上的癌症相关死亡是由转移引起的。在上皮性癌中，转移进展的一个关键过程是上皮到间充质转化样（EMT）向侵袭性细胞表型转变的表观遗传重编程。在非上皮性癌症中，不同的机制必然是转移性变化的基础，但对相关因素的了解相对较少。在这里，我们发现染色质调节SIRT7因子是上皮细胞和间充质癌细胞转移表型的关键调节因子。在上皮性前列腺癌中，高SIRT7水平与侵袭性癌症表型、转移性疾病和患者预后不良相关，SIRT7的缺失可以将这些细胞重编程为侵袭性较低的表型。有趣的是，SIRT7对于维持非上皮性肉瘤细胞的侵袭性和转移潜力也很重要。此外，SIRT7失活可以显著抑制癌细胞在体内的转移，而不依赖于原发肿瘤生长的变化。在机制上，我们还发现了SIRT7与其家族成员SIRT1之间的新联系，首次证明了两种哺乳动物sirtuins之间的直接相互作用和功能相互作用。结合之前的研究，我们的发现强调了SIRT7在维持多种癌症转移细胞表型中的广泛作用。
Metastasis is responsible for over 90% of cancer-associated mortality. In epithelial carcinomas, a key process in metastatic progression is the epigenetic reprogramming of an epithelial-to-mesenchymal transition-like (EMT) change towards invasive cellular phenotypes. In non-epithelial cancers, different mechanisms must underlie metastatic change, but relatively little is known about the factors involved. Here, we identify the chromatin regulatory Sirtuin factor SIRT7 as a key regulator of metastatic phenotypes in both epithelial and mesenchymal cancer cells. In epithelial prostate carcinomas, high SIRT7 levels are associated with aggressive cancer phenotypes, metastatic disease, and poor patient prognosis, and depletion of SIRT7 can reprogram these cells to a less aggressive phenotype. Interestingly, SIRT7 is also important for maintaining the invasiveness and metastatic potential of non-epithelial sarcoma cells. Moreover, SIRT7 inactivation dramatically suppresses cancer cell metastasis in vivo, independent of changes in primary tumor growth. Mechanistically, we also uncover a novel link between SIRT7 and its family member SIRT1, providing the first demonstration of direct interaction and functional interplay between two mammalian sirtuins. Together with previous work, our findings highlight the broad role of SIRT7 in maintaining the metastatic cellular phenotype in diverse cancers.
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影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
影响因子：
8.8
作者：
Simic P;Williams EO;Bell EL;Gong JJ;Bonkowski M;Guarente L
通讯作者：
Guarente L
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
64.8
作者：
Barber, Matthew F.;Michishita-Kioi, Eriko;Xi, Yuanxin;Tasselli, Luisa;Kioi, Mitomu;Moqtaderi, Zarmik;Tennen, Ruth I.;Paredes, Silvana;Young, Nicolas L.;Chen, Kaifu;Struhl, Kevin;Garcia, Benjamin A.;Gozani, Or;Li, Wei;Chua, Katrin F.
通讯作者：
Chua, Katrin F.
影响因子：
82.9
作者：
通讯作者：
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