Figure 2.

Graphical representation of intracellular CD44 and STAT3 interactions in various cancer models. Full-length CD44 can translocate to the nucleus via endosomal sorting and form nuclear complexes with histone acetyltransferase p300 and STAT3, which supports STAT3 phosphorylation and acetylation and subsequent pro-tumorigenic gene induction. Membrane-bound CD44 isoforms are capable of inducing canonical JAK-mediated STAT3 activation by critical tyrosine 705 phosphorylation, leading to either classical activated STAT3 dimer formation and target gene induction, or formation of nuclear NF-kB and STAT3 complex critical for cancer stem cell gene expression. Finally, HA-mediated CD44 activation has been shown to promote cytoplasmic NANOG/STAT3 complex formation involved in multiple drug resistance gene upregulation and chemoresistance.