title: SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung             metastasis of breast cancer in mice.
abstract: Silent information regulator 2 (SIR2) is a highly conserved protein, the             mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1             is involved not in only longevity due to caloric restriction but in a variety             of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration.             However, accumulating evidence shows that SIRT1 is overexpressed in various types             of malignant cells, and its inhibitors suppress the growth of tumor cells. The             relationship between SIRT1 and metastasis remains to be clarified. Here, we examined             the effect of SRT1720, a SIRT1 activator, on lung metastasis of breast cancer             cells. 4T1 breast cancer cells were subcutaneously implanted into syngeneic BALB/c             mice and SRT1720 was administered alone or with an antitumor agent, cisplatin.             As expected, cisplatin decreased the lung metastasis score, whereas SRT1720 increased             metastasis irrespective of cisplatin. In the primary tumors, cisplatin suppressed             the mRNA level of angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting             gene product of breast cancer, but SRT1720 reduced the effectiveness of cisplatin.             The results obtained with animal experiments were in accordance with those in             human cancer cells; SRT1720 significantly increased the amount of VEGF secreted             from MDA-MB-231 cells. Moreover, a transendothelial cell migration assay showed             that SRT1720 promotes the migration of MDA-MB-231 cells across an endothelial             cell layer despite the presence of cisplatin. These findings imply that SRT1720             promotes the pulmonary metastasis of breast cancer cells and SIRT1 may be an important             target for suppressing metastasis to the lung.
authors.affiliation: First Department of Internal Medicine, University of Toyama,                     Toyama 930-0194, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hayashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Imanishi
authors.forename: Toru
authors.initials: T
authors.lastname: Yamada
authors.forename: Minehiko
authors.initials: M
authors.lastname: Inomata
authors.forename: Toshiro
authors.initials: T
authors.lastname: Miwa
authors.forename: Shoko
authors.initials: S
authors.lastname: Matsui
authors.forename: Isao
authors.initials: I
authors.lastname: Usui
authors.forename: Masaharu
authors.initials: M
authors.lastname: Urakaze
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuya
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D006576:Heterocyclic Compounds, 4 or More Rings; D012333:RNA, Messenger; C525422:SRT1720; D042461:Vascular Endothelial Growth Factor A; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D002945:Cisplatin