Plasminogen activator inhibitor 1 - insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence

被引：115

作者：

Elzi, David J. ^{[1
]}

Lai, Yanlai ^{[1
]}

Song, Meihua ^{[1
]}

Hakala, Kevin ^{[2
]}

Weintraub, Susan T. ^{[2
,3
]}

Shiio, Yuzuru ^{[1
,2
,3
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 30期

基金：

美国国家卫生研究院;

关键词：

chemotherapy; isotope; coded affinity tag; protease; protease inhibitor; protein secretion; QUANTITATIVE PROTEOMIC ANALYSIS; CODED AFFINITY TAGS; REPLICATIVE SENESCENCE; INDUCTION; FIBROBLASTS; CELLS; P53; GENE; CULTURE;

D O I：

10.1073/pnas.1120437109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Cellular senescence is widely believed to play a key role in tumor suppression, but the molecular pathways that regulate senescence are only incompletely understood. By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment. The senescence-inducing activity of IGFBP3 is inhibited by tissue-type plasminogen activator-mediated proteolysis, which is counteracted by plasminogen activator inhibitor 1 (PAI-1), another secreted mediator of senescence. We demonstrate that IGFBP3 is a critical downstream target of PAI-1-induced senescence. These results suggest a role for an extracellular cascade of secreted proteins in the regulation of cellular senescence.

引用

页码：12052 / 12057

页数：6

共 29 条

[1]

Human pregnancy serum contains at least two distinct proteolytic activities with the ability to degrade insulin-like growth factor finding protein-3 [J].