Journal article
Matrix-independent Survival of Human Keratinocytes through an EGF Receptor/MAPK-Kinase-dependent Pathway
Molecular biology of the cell, v 12(5), pp 1519-1527
May 2001
PMID: 11359940
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Normal epithelial cells undergo apoptosis when they are denied contact with the extracellular matrix, in a process termed “anoikis.” Conversely, malignant epithelial cells typically acquire anchorage independence, i.e., the capacity to survive and grow in the absence of matrix interaction. Here we asked the question whether anoikis is affected by signaling through the EGF receptor (EGFR). We focused on the EGFR because EGFR signaling is frequently deregulated in malignant epithelial cells. We demonstrate that EGFR activation markedly alleviated the requirement of matrix engagement for survival of primary and immortalized human keratinocytes in suspension culture. Protection of epithelial cells through EGFR activation against anoikis was associated with and required sustained MAPK phosphorylation during the early phase of suspension culture. Interestingly, high levels of MAPK phosphorylation were not only required for EGFR-mediated protection against anoikis but also occurred as a consequence of caspase activation at later stages of suspension culture. These results demonstrate that EGFR activation contributes to anchorage-independent epithelial cell survival and identify MAPK activation as an important mechanism in this process.
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Details
- Title
- Matrix-independent Survival of Human Keratinocytes through an EGF Receptor/MAPK-Kinase-dependent Pathway
- Creators
- Monika Jost - Department of Dermatology and Cutaneous Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Teresa M Huggett - Department of Dermatology and Cutaneous Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Csaba Kari - Department of Dermatology and Cutaneous Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Ulrich Rodeck - Department of Dermatology and Cutaneous Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
- Contributors
- Martin Schwartz (Editor)
- Publication Details
- Molecular biology of the cell, v 12(5), pp 1519-1527
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Intensive Medical Sciences (IMS)
- Web of Science ID
- WOS:000170350100026
- Scopus ID
- 2-s2.0-0034768547
- Other Identifier
- 991014878171604721
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- Web of Science research areas
- Cell Biology