CLDN6

CLDN6 is a tight-junction claudin that supports epithelial differentiation by triggering epithelial morphogenesis in mouse F9 and embryonic stem cells^[1]. Mechanistically, CLDN6-mediated cell-cell adhesion activates SFK/PI3K/AKT signaling and stimulates nuclear receptor activity, linking junctional adhesion to transcriptional regulation^[2]. In gastric cancer models, CLDN6 promotes proliferation and invasion through the Hippo-YAP1-Snail1 axis, including reduced LATS1/2 and YAP1 phosphorylation and enhanced EMT-related signaling^[3]. In breast cancer cells, however, CLDN6 suppresses proliferation, migration, and invasion by inhibiting ERK/Sp1/cyclin D1 and ERK/IL-8 signaling, indicating context-dependent experimental effects^[4]. Compared with related isoforms, CLDN6 and CLDN9, but not CLDN1, can function as additional hepatitis C virus entry coreceptors, while other tested claudins lacked this activity. This isoform issue is central for reagent design because rare monoclonal antibodies bound CLDN6 with minimal cross-reactivity against CLDN9 and 22 other claudin family members^[5]. For applications, immunologic and chemical targeting of CLDN6 eliminated tumorigenic human pluripotent stem cells from mixed cultures, supporting its use in stem-cell safety research^[6]. In clinical translation, CLDN6 CAR-T cells with or without an amplifying RNA vaccine were evaluated in relapsed or refractory CLDN6-positive solid tumors^[7].