SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis

Xiaolong Tang, Lei Shi, Ni Xie, Zuojun Liu, Minxian Qian, Fanbiao Meng, Qingyang Xu, Mingyan Zhou, Xinyue Cao, Wei-Guo Zhu and Baohua Liu ()
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Xiaolong Tang: Shenzhen University Health Science Center
Lei Shi: Shenzhen University Health Science Center
Ni Xie: First Affiliated Hospital of Shenzhen University
Zuojun Liu: Shenzhen University Health Science Center
Minxian Qian: Shenzhen University Health Science Center
Fanbiao Meng: Shenzhen University Health Science Center
Qingyang Xu: Shenzhen University Health Science Center
Mingyan Zhou: Shenzhen University Health Science Center
Xinyue Cao: Shenzhen University Health Science Center
Wei-Guo Zhu: Shenzhen University Health Science Center
Baohua Liu: Shenzhen University Health Science Center

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00396-9

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