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Vol. 12, Issue 5, 1519-1527, May 2001
Department of Dermatology and Cutaneous Biology and the Kimmel
Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
19107
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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