Wnt antagonist SFRP1 functions as a secreted mediator of Senescence

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

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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