Figure 2.

The function of non-TJ CLDN4. (A) CLDN4 monomer that does not form TJs is a binding partner for integrin β1 expressed in neighboring tumor cells, activates FAK, and promotes expression of stemness-associated genes. (B) CLDN4 translocates into the cytoplasm from TJs disrupted by CPE and forms a stable complex with TAZ, MST, LATS, and ZO1, but YAP is released from the complex and translocates into the nucleus with ZO2 to induce expression of YAP target genes, leading to proliferation and EMT. (C) EphA2 activated by Ephrin A1 expressed on the surface of neighboring cells phosphorylates CLDN4 and releases it from TJs. The released CLDN4 is translocated into the nucleus with YAP. CLDN4, claudin-4; TJ, tight junction; CPE, Clostridium perfringens enterotoxin; TAZ, tafazzin; YAP, yes-associated protein; ZO, zonula occludens; MST, mammalian Ste20-like kinase; LATS, large tumor suppressor kinase; Eph A2, ephrin type-A receptor 2; FAK, focal adhesion kinase; EMT, epithelial-mesenchymal transition.