Tenascin-covered beads bind cells (top) unless an antibody to EGFR is present (bottom).

Continuing to stretch the bounds of what the extracellular matrix is known to do, Swindle et al. (page 459) show that tenascin-C, a matrix protein, can signal through the epidermal growth factor receptor (EGFR). The authors suggest that the distinction between receptor interactions that lead to signaling and those that anchor the cell in the environment may be far more tenuous than commonly thought.

Tenascin-C is found in the surrounding matrix when cells are actively dividing and moving: for example, during embryonic development, wound healing, and in invasive cancers. These are also occasions when EGFR is known to be activated. Its previously known ligands are soluble proteins. The study used cells that lack endogenous EGFR ligands to show that tenascin-C, and specifically its EGF-like repeats, activate EGFR in a dose-dependent...

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