CD44 is a multidomain signaling platform that integrates extracellular matrix cues with growth factor and cytokine signals.

The reception and integration of the plethora of signals a cell receives from its microenvironment is decisive in determining cell behavior. Perturbation of extracellular cues, or an inappropriate response to or integration of these signals lies at the root of many diseases such as cancer. The transmembrane protein CD44 contributes to the reception of a broad variety of microenvironmental components, including extracellular matrix constituents such as hyaluronic acid, as well as growth factors and cytokines. In this chapter, we review the range of extracellular cues that are recognized by CD44, and show how CD44 serves to integrate this information at several levels through the mechanisms by which it contributes to transduction of these various microenvironmental signals.