SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis.
SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis.
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SIRT7 拮抗 TGF-β 信号传导并抑制乳腺癌转移
DOI：
10.1038/s41467-017-00396-9
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发表时间：
2017-08-22
影响因子：
16.6
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Tang X;Shi L;Xie N;Liu Z;Qian M;Meng F;Xu Q;Zhou M;Cao X;Zhu WG;Liu B
远处转移是乳腺癌相关死亡的主要原因，然而针对转移的有效治疗策略仍然很少。这在很大程度上归因于转移过程中肿瘤内的时空异质性。在这里，我们发现蛋白脱乙酰酶SIRT7在人和小鼠的乳腺癌肺转移中显著下调，并预测无转移生存。SIRT7缺乏促进乳腺癌细胞转移，而在多瘤病毒中T抗原乳腺癌模型中，SIRT7的瞬时表达抑制转移。在机制上，SIRT7去乙酰化并促进β-TrCP1介导的Smad4降解，SIRT7缺乏激活转化生长因子-β信号通路，促进上皮向间充质转化。值得注意的是，白藜芦醇激活SIRT7脱乙酰酶活性，抑制乳腺癌肺转移，并提高存活率。我们的数据显示SIRT7作为转化生长因子-β信号的调节器和乳腺癌转移的抑制因子，同时提供了一种有效的抗转移治疗策略。转移性疾病是乳腺癌相关死亡的主要原因；因此，需要更好地了解这一过程及其参与者。在此，作者报道了SIRT7在抑制Smad4介导的乳腺癌转移中的作用，提供了一条可能的治疗途径。
Distant metastasis is the main cause of breast cancer-related death; however, effective therapeutic strategies targeting metastasis are still scarce. This is largely attributable to the spatiotemporal intratumor heterogeneity during metastasis. Here we show that protein deacetylase SIRT7 is significantly downregulated in breast cancer lung metastases in human and mice, and predicts metastasis-free survival. SIRT7 deficiency promotes breast cancer cell metastasis, while temporal expression of Sirt7 inhibits metastasis in polyomavirus middle T antigen breast cancer model. Mechanistically, SIRT7 deacetylates and promotes SMAD4 degradation mediated by β-TrCP1, and SIRT7 deficiency activates transforming growth factor-β signaling and enhances epithelial-to-mesenchymal transition. Significantly, resveratrol activates SIRT7 deacetylase activity, inhibits breast cancer lung metastases, and increases survival. Our data highlight SIRT7 as a modulator of transforming growth factor-β signaling and suppressor of breast cancer metastasis, meanwhile providing an effective anti-metastatic therapeutic strategy. Metastatic disease is the major reason for breast cancer-related deaths; therefore, a better understanding of this process and its players is needed. Here the authors report the role of SIRT7 in inhibiting SMAD4-mediated breast cancer metastasis providing a possible therapeutic avenue.
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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：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
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.