Wnt antagonist SFRP1 functions as a secreted mediator of Senescence

David J. Elzi, Meihua Song, Kevin Hakala, Susan E Weintraub, Yuzuru Shiioa

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4388-4399
Number of pages12
JournalMolecular and Cellular Biology
Volume32
Issue number21
DOIs
StatePublished - Nov 2012

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Cell Aging
Retinoblastoma
DNA Damage
Neoplasms
Oxidative Stress
frizzled related protein-1
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wnt antagonist SFRP1 functions as a secreted mediator of Senescence. / Elzi, David J.; Song, Meihua; Hakala, Kevin; Weintraub, Susan E; Shiioa, Yuzuru.

In: Molecular and Cellular Biology, Vol. 32, No. 21, 11.2012, p. 4388-4399.

Research output: Contribution to journalArticle

Elzi, David J. ; Song, Meihua ; Hakala, Kevin ; Weintraub, Susan E ; Shiioa, Yuzuru. / Wnt antagonist SFRP1 functions as a secreted mediator of Senescence. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 21. pp. 4388-4399.
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