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SIRT7 antagonizes TGF-ß signaling and inhibits breast cancer metastasis.
Tang, Xiaolong; Shi, Lei; Xie, Ni; Liu, Zuojun; Qian, Minxian; Meng, Fanbiao; Xu, Qingyang; Zhou, Mingyan; Cao, Xinyue; Zhu, Wei-Guo; Liu, Baohua.
Afiliação
  • Tang X; Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Shi L; Center for Anti-aging and Regenerative Medicine, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Xie N; Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Liu Z; Center for Anti-aging and Regenerative Medicine, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Qian M; Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
  • Meng F; Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Xu Q; Center for Anti-aging and Regenerative Medicine, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Zhou M; Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Cao X; Center for Anti-aging and Regenerative Medicine, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Zhu WG; Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • Liu B; Center for Anti-aging and Regenerative Medicine, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Nat Commun ; 8(1): 318, 2017 08 22.
Article em En | MEDLINE | ID: mdl-28827661
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 ß-TrCP1, and SIRT7 deficiency activates transforming growth factor-ß 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-ß 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Fator de Crescimento Transformador beta / Sirtuínas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Fator de Crescimento Transformador beta / Sirtuínas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: China