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Mol Cell Biol. 2012 Nov;32(21):4388-99. doi: 10.1128/MCB.06023-11. Epub 2012 Aug 27.

Wnt antagonist SFRP1 functions as a secreted mediator of senescence.

Author information

1
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.

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.

PMID:
22927647
PMCID:
PMC3486147
DOI:
10.1128/MCB.06023-11
[Indexed for MEDLINE]
Free PMC Article

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