Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.
Mol Cell Biol. 2012 Nov;32(21):4388-99. doi: 10.1128/MCB.06023-11. Epub 2012 Aug 27.
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.
近年来，细胞衰老已成为一种重要的肿瘤抑制机制，但人们对衰老的发生机制知之甚少。在这里，我们报告称，分泌型卷曲相关蛋白 1（SFRP1）是 Wnt 信号的一种分泌型拮抗剂，在由 DNA 损伤或氧化应激引起的细胞衰老过程中会过度分泌。SFRP1 是这些因素引起的应激诱导衰老所必需的，并且足以诱导衰老表型。我们提供的证据表明，SFRP1 通过抑制 Wnt 信号和激活视网膜母细胞瘤（Rb）途径来作为衰老的分泌介质发挥作用，并且与癌症相关的 SFRP1 突变体不能诱导衰老。
