Claudin-4–adhesion signaling drives breast cancer metabolism and progression via liver X receptor β

Cell adhesion molecules exhibit the signaling abilities to control a variety of physiological and pathological processes; however, the underlying molecular basis remains poorly defined. Here, we demonstrate that the claudin-4 (CLDN4)-adhesion signaling accelerates breast cancer metabolism and progression via the nuclear receptor LXRb (liver X receptor b). Knockout and rescue experiments revealed that the CLDN4 signaling targets S432 in LXRb, leading to enhanced cell proliferation and tumor growth in breast cancer cells. In addition, RT-qPCR analysis showed the CLDN4-regulated genes are classified into at least six groups by distinct LXRb- and LXRbS432-dependence. Collectively, our results provide a link between cell adhesion and nuclear receptor signalings to coordinate cancer metabolism and advancement. RNA-seq analysis was performed using wild-type and CLDN4-knockout breast cancer cell lines (T47D and MCF7).