The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.Gastric carcinoma (GC) slowly metastasizes to the lymph nodes, liver, peritoneum, and ovary. 1,2 Poor prognostic features associated with gastrointestinal (GI) tumors in the ovary characterize GC metastasis to the ovary, referred to as Krukenberg tumor. Krukenberg tumor is established via blood or lymphatic vessels and displays abundant mucinfilled signet ring cells and diffuse sarcomatoid proliferation of ovarian stroma. 3-8 Despite the high incidence, an orthotopic mouse model that can recapitulate the GC or Krukenberg tumor pathobiology has not been established. In addition, genes involved in GC metastasis have not been systematically investigated in an appropriate model, necessitating the development of animal models that represent the process of secondary organ metastasis in human GC. Primary tumors invade into neighboring blood vessels, usually, by undergoing a loss of epithelial and gain of mesenchymal characteristics (epithelial-mesenchymal transition, EMT), which drives the motility and early behavior of invasive carcinomas. 9 In contrast, in the metastasized organs, a gain of epithelial and loss of mesenchymal characteristics (mesenchymal-epithelial transition, MET) can occur, and is likely correlated with the extravasation or colonization of cancer cells.Although, the expression of GAGE genes is limited to germ cells in healthy individuals, members of the GAGE gene family are anti-apoptotic proteins that modulate apoptotic regulators. Therefore, it has been suggested to have potential roles in cancer, 10,11 and is, in fact deregulated in a wide range of cancers. 12,13 GAGE gene expression correlates with poor prognosis in gastric cancer, esophageal carcinoma, and neuroblastoma. 14-16 However, little is known about thei...