Adhesion and Penetration: Two sides of CD44 signal transdcution cascades in the context of cancer cell metastasis

Publisher Summary CD44 is a cell-surface glycoprotein receptor with a well-defined HA binding domain within its amino-terminal ectodomain. Expression of CD44 on the surface of cancer cells facilitates their adhesion to other cells and the avidity with which they may adhere to substituents of the extracellular matrix. In addition to regulating adhesion, CD44 facilitates the penetration of cancer cells through tissue by acting as a scaffold to concentrate proteases on the invasive surface of cells and by regulating protease expression in cancer cells. This chapter focuses on how one of the principal HA receptors, CD44, is associated with conferring the malignant progression of tumor cells, by contributing to the modulation of cancer cell adhesion and cancer cell invasion within the tumor microenvironment. The experimental observations in cell-based studies provide evidence to implicate HA-induced CD44 signaling in conferring many of the properties essential for tumor cells to successfully negotiate each of the defined stages of the metastatic cascade. The chapter provides a schematic depiction of the role played by CD44 in regulating and coordinating proteolytic-dependent invasion of cancer cells through extracellular matrix. The role of CD44 in contributing to cell–cell adhesion is confirmed by studies from several laboratories examining both its physiological and pathophysiological significance. Expression of CD44 in multiple tumor types typically correlates with an increased metastatic capability as opposed to directing tissue-specific metastasis.