title: Wnt antagonist SFRP1 functions as a secreted mediator of senescence.
abstract: Cellular senescence has emerged as a critical tumor suppressive mechanism in recent years, but relatively little is known about how senescence occurs. Here, we report that secreted Frizzled-related protein 1 (SFRP1), a secreted antagonist of Wnt signaling, is oversecreted upon cellular senescence caused by DNA damage or oxidative stress. SFRP1 is necessary for stress-induced senescence caused by these factors and is sufficient for the induction of senescence phenotypes. We present evidence suggesting that SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma (Rb) pathway and that cancer-associated SFRP1 mutants are defective for senescence induction.
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elzi
authors.forename: Meihua
authors.initials: M
authors.lastname: Song
authors.forename: Kevin
authors.initials: K
authors.lastname: Hakala
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Shiio
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D004249:DNA Damage; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; D051153:Wnt Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins