Interaction of N ecl‐4/ CADM 4 with E rb B 3 and integrin α 6 β 4 and inhibition of E rb B 2/ E rb B 3 signaling and hemidesmosome disassembly

Nectin‐like molecule 4 ( N ecl‐4)/ CADM 4, a transmembrane cell–cell adhesion molecule with three Ig‐like domains, was shown to serve as a tumor suppressor, but its mode of action has not been elucidated. In this study, we showed that N ecl‐4 interacted in cis with E rb B 3 through their extracellular regions, recruited PTPN 13 and inhibited the heregulin‐induced activation of the E rb B 2/ E rb B 3 signaling. In addition, we extended our previous finding that N ecl‐4 interacts in cis with integrin α 6 β 4 through their extracellular regions and found that N ecl‐4 inhibited the phorbol ester‐induced disassembly of hemidesmosomes. These results indicate that N ecl‐4 serves as a tumor suppressor by inhibiting the E rb B 2/ E rb B 3 signaling and hemidesmosome disassembly.