Pancreatic cancer stem cell markers and exosomes - the incentive push

Figure 5 The EpCAM-palmitoylated claudin7 complex in pancreatic cancer stem cells. Upon palmitoylation the TJ protein cld7 becomes excluded from TJ and recruited into GEM, where it associates with monomeric EpC. Monomeric EpC becomes susceptible to GEM-located TACE and PSN2. EpICD associates with β-catenin and translocates to the nucleus acting as a cotranscription factor for c-myc, cyclinD1 and several EMT genes. The cld7-TACE-PSN2 complex also contributes to NOTCH cleavage. NICD contributes to HES activation, which inhibits Pten transcription. The palmitoylated cld7-uPAR association promotes integrin activation and transcription of EMT genes via ILK. Activation of the JNK pathway contributes to inhibition of Pten transcription. In Pa-CSC EpC becomes cleaved and involved in EMT gene transcription; palmitoylated cld7 additionally is engaged via Notch cleavage and integrin activation in apoptosis resistance. CSC: Cancer stem cells; GEM: Glycolipid-enriched microdomains; ILK: integrin-linked kinase; TJ: Tight junction; HSP: Heat shock protein; PKC: Phophokinase C; TACE: TNFα converting enzyme.