EGFR-Dependent Regulation of Matrix-Independent Epithelial Cell Survival
Abstract
Background: Signaling through the epidermal growth factor (EGFR) has been implicated in both effective wound healing and epithelial neoplasia. We have identified a novel function of the EGFR in support of epithelial cell survival, particularly in conditions of anchorage-independence. Objective/Hypothesis: Define molecular mechanisms and pathways by which EGFR activation supports epithelial cell survival. Two specific aims focus on (1) posttranslational modification of relevant Bcl-2 family members by EGFR activation through MAPK-dependent mechanisms and, (2) STAT3 activation by deregulated EGFR signaling as observed in epithelial cancer. Progress: Significant progress relating to Specific Aim I has included: Publication of results in support of BIM regulation by the EGFR in normal and transformed keratinocytes (Appendices included); Characterization of a role of NF-KB activation in keratinocyte survival in the absence of extracellular matrix interaction; and Pro-apoptotic signals by JNK and p38 activation in the anchorage-independent state are counteracted by NF-kB activity. We have completed the work proposed in Specific Aim 2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA463929
Entities
People
- Ulrich Rodeck
Organizations
- Thomas Jefferson University