Ca2+ is known to have an important role in cellular migration, invasion and motility via the regulation of various kinases,42 including calpain, which results in the proteolysis of E-cadherin.43 Our findings demonstrate that S100A14 may inactivate calpain through blocking the Ca2+ influx, resulting in the upregulation of E-cadherin, which serves as a differentiation marker and prevents GC metastasis.33, 44 In accordance with the function of LKB1,21 GATA-322 and RARRES3,45 S100A14 inhibits tumor metastasis by regulating differentiation and adhesion in GC. Here, S100A14 is linked to gastric cancer.