Noncanonical signal transduction downstream of the GDNF-GFRA1 axis is achieved by affecting the concentration of intracellular second messengers (calcium ions), which in turn regulate lysosomal function, maintain the level of autophagic flux under metabolic stress, help tumor cells to survive and colonize in the metastatic microenvironment of the liver and, ultimately, promote the occurrence and development of GC liver metastases [49, 50]. This evidence concerns the gene GDNF and gastric cancer.