ArticleThe Journal of experimental medicine2003
Tumors acquire inhibitor of apoptosis protein (IAP)-mediated apoptosis resistance through altered specificity of cytosolic proteolysis.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 67 citations in OpenAlex.
- Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.ACS pharmacology & translational science · 2021Review
- Effects of ionizing radiation on the viability and proliferative behavior of the human glioblastoma T98G cell line.BMC research notes · 2018Article
- Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells.Oxidative medicine and cellular longevity · 2018Article
- XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.Theranostics · 2018Article
- Inducing death in tumor cells: roles of the inhibitor of apoptosis proteins.F1000Research · 2017Review
- Article
- Tripeptidyl peptidase II in human oral squamous cell carcinoma.Journal of cancer research and clinical oncology · 2013Article
- Post-proteasomal and proteasome-independent generation of MHC class I ligands.Cellular and molecular life sciences : CMLS · 2011Review
- The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping and Stress.Journal of oncology · 2010Article
- Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation.British journal of cancer · 2009Article
- Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- High Smac/DIABLO expression is associated with early local recurrence of cervical cancer.BMC cancer · 2006Article
- The proteasome is required for rapid initiation of death receptor-induced apoptosis.Molecular and cellular biology · 2006Article
- Molecular architecture and assembly mechanism of Drosophila tripeptidyl peptidase II.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- SMAC is expressed de novo in a subset of cervical cancer tumors.BMC cancer · 2004Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many tumors overexpress members of the inhibitor of apoptosis protein (IAP) family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that tumor cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing tumors. Survival of tumor cells with low proteasomal activity can occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves tumor cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing tumors in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo tumors, that these have acquired an altered peptidase activity, with up-regulation of TPP II activity and decreased proteasomal activity. Importantly, we find that growth of subcutaneous tumors is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives tumor progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical tumors that have increased levels of IAP molecules.
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