Graphene oxide induces canonical Wnt/β-catenin signaling-dependent toxicity in Caenorhabditis elegans

The potential adverse effects of graphene oxide (GO) on organisms have received great attention. However, the underlying molecular mechanisms for response to GO exposure are still largely unclear. Canonical Wnt/β-catenin signaling is an evolutionarily conserved signaling, and plays a key role in the development. Using assay system of Caenorhabditis elegans, we investigated the potential involvement of canonical Wnt/β-catenin signaling pathway in the regulation of response to GO. GO exposure caused the damage on the functions of both primary and secondary targeted organs by dysregulating the expression of β-catenin BAR-1, APR-1 and GSK-3 in APC complex, Dishevelled proteins of DSH-1, and DSH-2, and Frizzled receptors of MOM-5 and CFZ-2 in the Wnt/β-catenin signaling pathway. Based on genetic evidence, we further raised a signaling cascade of MOM-5/CFZ-2-DSH-1/DSH-2-APR-1/GSK-3-BAR-1 in the Wnt/β-catenin signaling pathway in the regulation of GO toxicity. The homeobox protein EGL-5, an important downstream target of Wnt/β-catenin signaling, regulated GO toxicity by modulating expression of the genes required for the control of oxidative stress. Moreover, β-catenin BAR-1 acted in parallel with insulin or p38 MAPK signaling to regulate the GO toxicity. Therefore, our results suggest the crucial function of Wnt/β-catenin signaling pathway in the regulation of GO toxicity in organisms.