@article{c4099051d321416c8b8c523bad9b1ba6,
title = "Halting neuroblastoma metastasis by controlling integrin-mediated death",
abstract = "Neuroblastoma, a common tumor of nervous system origin in young children, is usually detected only after the primary tumor has metastasized and the chances of its complete removal are low. Metastatic neuroblastoma cells commonly suppress expression of the gene encoding caspase-8. In a neuroblastoma murine model, expression of caspase-8 and integrin α3β1 was dramatically reduced during tumor development. Analysis of clinical biopsies supported the observation that expression of both genes is low in human patients with metastatic disease. These data suggest that loss of expression of both caspase-8 and unligated integrins contribute to the survival of tumor cells migrating from the primary tumor. Integrin receptors that are unable to find appropriate ligands can form a large molecular complex containing caspase-8, explaining why cells that have diminished expression of either of these two genes have a significant survival advantage in foreignmicroenvironments. Thus, upregulating expression of caspase-8 and integrins, or alternatively, antagonizing integrins within the primary tumor may be important therapeutically in halting neuroblastoma metastasis.",
author = "Tal Teitz and Stupack, {Dwayne G.} and Lahti, {Jill M.}",
note = "Funding Information: Caspase-8 has been linked to integrin-mediated regulation of apoptosis.17-18 Integrins, cell surface proteins that mechanically link the extracellular matrix (ECM) and the cells{\textquoteright} interior, also transduce biochemical signals that modulate diverse processes including cell survival, migration, growth, and differentiation.19-20 Ligation of integrins to immobilized ECM proteins leads to transduction of intracellular signals that govern processes such as This work was supported by funds from the National cell migration and survival.21-22 Cells express different integrin heterodimers whose ligand Cancer Institute CA67938, Cancer Center support specificity is based on the pairing of particular α and β subunits. For example, α3 integrin Grant CA21765, and the American Syrian Lebanese only pairs with β1 and the combination forms a receptor for laminins. Cells tend to Associated Charities (ALSAC) to J.M.L., and NIH express integrins appropriate for interaction and survival within their microenvironment. grant CA107263 to D.G.S. In an inappropriate environment integrins can serve as biosensors, promoting caspase-8-dependent apoptosis.23 In this form of programmed cell death, caspase-8 and unligated integrin β1 subunits are recruited to a molecular complex at or near the cell{\textquoteright}s plasma membrane, leading to caspase-8 activation and cell death. Indeed, blockade of β1-integrin in human kertinocytes has recently been shown to trigger cell death by activation of caspase-8.24 Downregulation of either integrins or caspase-8 blocks this biosensory function {\textcopyright}2006 LANDES BIOSCIENCE and promotes resistance to cell-death, thereby enhancing metastasis.",
year = "2006",
month = apr,
day = "1",
doi = "10.4161/cc.5.7.2615",
language = "English (US)",
volume = "5",
pages = "681--685",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "7",
}