Wnt antagonist SFRP1 functions as a secreted mediator of senescence

Elzi DJ, Song M, Hakala K, Weintraub ST, Shiio Y
Source: Mol Cell Biol
Publication Date: (2012)
Issue: 32(21): 4388-99
Research Area:
Basic Research
Cells used in publication:
Epithelial, mammary, human (HMEC)
Species: human
Tissue Origin: breast
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.