Claudin 4 enhances the malignancy of glioma cells via NNAT/Wnt signaling

Gliomas are the most common malignancies of the central nervous system and are associated with high mortality rates. However, the pathogenesis of gliomas is unclear. In this study, we show that elevated claudin-4 (CLDN4) levels in glioma tissues are associated with poor clinical outcomes. We found that upregulating the expression of CLND4 enhanced the proliferative and migratory capacities of glioma cells. Mechanistically, CLND4 upregulated Neuronatin (NNAT) by activating Wnt3A signaling, and aided in the progression of the glioma. Most importantly, our data demonstrated that CLND4 overexpression caused rapid tumor growth in mice injected with LN229 cells and reduced the survival of these mice. Our findings reveal that CLND4 modulates malignancy in glioma cells; targeting CLDN4 may open up new avenues for glioma treatment.