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SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis.
- Source :
-
Nature communications [Nat Commun] 2017 Aug 22; Vol. 8 (1), pp. 318. Date of Electronic Publication: 2017 Aug 22. - Publication Year :
- 2017
-
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.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.
- Subjects :
- Animals
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line
Cell Line, Tumor
Down-Regulation
Epithelial-Mesenchymal Transition drug effects
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Lung Neoplasms genetics
Lung Neoplasms secondary
Mice, Inbred BALB C
Mice, Nude
Mice, Transgenic
RNA Interference
Signal Transduction
Sirtuins genetics
Smad4 Protein metabolism
Transforming Growth Factor beta pharmacology
Transplantation, Heterologous
Breast Neoplasms metabolism
Lung Neoplasms metabolism
Sirtuins metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28827661
- Full Text :
- https://doi.org/10.1038/s41467-017-00396-9