Work

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

Year: 2012

Type: article

Abstract: 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1120437109

Authors: David J. Elzi, Yanlai Lai, Meihua Song, Kevin Hakala, Susan T. Weintraub, Yuzuru Shiio

Institution: The University of Texas at San Antonio Health Science Center

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, University of Texas Health Science Center at San Antonio, National Institute on Aging, National Cancer Institute