Matrix-independent survival of human keratinocytes through an EGF receptor/MAPK-kinase-dependent pathway.

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.

journal_name

Mol Biol Cell

authors

Jost M,Huggett TM,Kari C,Rodeck U

doi

10.1091/mbc.12.5.1519

keywords:

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

1519-27

issue

5

eissn

1059-1524

issn

1939-4586

journal_volume

12

pub_type

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