Journal of Mammary Gland Biology and Neoplasia

, Volume 6, Issue 3, pp 287-297

CD44-Mediated Oncogenic Signaling and Cytoskeleton Activation During Mammary Tumor Progression

  • Lilly Y. W. BourguignonAffiliated withDepartment of Cell Biology and Anatomy, University of Miami Medical School

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CD44, a hyaluronan (HA)3 receptor, belongs to a family of transmembrane glycoproteins which exists as several isoforms. Cell surface expression of certain CD44 isoforms is closely correlated with the progression and prognosis of breast cancers. A number of angiogenic factors (e.g., VEGF and FGF-2) and matrix degrading enzymes (MMPs) are tightly complexed with CD44 isoforms, suggesting that they are involved in the onset of oncogenic signals required for breast tumor cell invasion and migration. Most importantly, interaction of extracellular matrix components (e.g., HA) with cells triggers the cytoplasmic domain of CD44 isoforms to bind its unique downstream effectors (e.g., the cytoskeletal protein ankyrin or various oncogenic signaling molecules-Tiam1, RhoA-activated ROK, c-Src kinase and p185HER2) and to coordinate intracellular signaling pathways (e.g., Rho/Ras signaling and receptor-linked/non-receptor-linked tyrosine kinase pathways), leading to a concomitant onset of multiple cellular functions (e.g., tumor cell growth, migration and invasion) and breast tumor progression.

CD44 oncogenic signaling ankyrin Rho GTPases breast tumor progression