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Go or Grow: How HA Controls the EGF Receptor
Author(s) -
Schroeder Joyce Ann,
Lopez Jose Ignacio,
Louderbough Jeanne Vangils
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.387.1
Subject(s) - cd44 , microbiology and biotechnology , mapk/erk pathway , extracellular matrix , epidermal growth factor , signal transduction , cell growth , cell , epidermal growth factor receptor , cell adhesion , focal adhesion , filopodia , cell migration , chemistry , biology , receptor , biochemistry , actin
The extracellular matrix (ECM) can govern epithelial cell behavior by influencing cellular invasion, a process which signals a deadly stage of cancer progression. In attempting to understand the role of the ECM in invasion, we previously found that the adhesion receptor CD44 protects against metastasis when cells are presented with hyaluronan (HA) embedded in Type I collagen. In our current studies, we have attempted to determine the mechanism by which CD44/HA interactions are inhibiting invasion. We have discovered that the inhibition of invasion provided by collagen‐embedded HA (eHA) occurs through the down‐regulation of both the Epidermal Growth Factor Receptor (EGFR) and PAK and corresponds with cell‐cell attachment and lamellopodia formation. Of significance is the observation that when HA is provided to cells in a soluble form (sHA), invasion is promoted and EGFR and PAK are both activated, corresponding to an inhibition of cell‐cell attachment and filopodia formation. Finally, we have found that these opposing effects of eHA versus sHA are further carried to the arena of proliferation, as eHA promotes proliferation and ERK MAP Kinase activity, while sHA inhibits each of these activities in the presence of collagen. Together, these data demonstrate that the form of HA presentation to the cell has a dramatic affect on its ability to alter cellular morphology, behavior and signal transduction events.