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EMT Phenotype is Induced by Increased Src Kinase Activity via Src-Mediated Caspase-8 Phosphorylation.
- Source :
-
Cellular Physiology & Biochemistry (Karger AG) . 2012, Vol. 29 Issue 3/4, p341-352. 12p. - Publication Year :
- 2012
-
Abstract
- Caspase-8 governs multiple cell responses to the microenvironmental cues. However, its integration of 'death-life' signalings remains elusive. In our study, the role of caspase-8-Src is well-established as a promoter for migration or metastasis in Casp8+Src+ A549/H226 cells in vivo and in vitro. In particular for nude mice models, mice implanted with Casp8+Src+ A459/H226 cells remarkably increased spontaneous tumor metastatic burden with a significant survival disadvantage. Additionally, we detect that Src-mediated caspase-8 phosphorylation stimulates Src phosphorylation at Tyr-416 via the linkage of Src SH2 domain with phosph-Tyr-380 site of caspase-8. In turn, activated Src can efficiently induce epithelial-mesenchymal transition (EMT) phenotypic features to promote tumor cells metastasis. Surprisingly, RXDLL motif deletion in the DEDa of caspase-8 attenuates tumor cell migration or metastasis via impairing the recruitment of caspase-8 into the cellular periphery where activated Src is subject to caspase-8 phosphorylation. Together, a simple model is that the peripherization of caspase-8 is well-poised to facilitate Src-mediated caspase-8 phosphrylation at Tyr-380, then binding of phospho-Tyr380 of caspase-8 to Src SH2 domain may maintain Src in an active conformation to induce EMT phenotype, a key step toward cancer metastasis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10158987
- Volume :
- 29
- Issue :
- 3/4
- Database :
- Academic Search Index
- Journal :
- Cellular Physiology & Biochemistry (Karger AG)
- Publication Type :
- Academic Journal
- Accession number :
- 74304273
- Full Text :
- https://doi.org/10.1159/000338489