FAM126A interacted with ENO1 mediates proliferation and metastasis in pancreatic cancer via PI3K/AKT signaling pathway.

Abstract

Pancreatic cancer (PC) is a common digestive system carcinoma with high mortality rate mostly due to aberrant growth and distant metastasis. Current researches demonstrated that Family Sequence Similarities (FAMs) have been involving in tumor development, and which subfamily has the function of promoting or inhibiting tumors and its in-depth molecular mechanism remains unclear. Based on the Gene Expression Omnibus (GEO), the Gene Expression Profiling Interactive Analysis (GEPIA2), we observed that FAM126A is in high expressed level among PC tissues and contributes to worse progression of PC, which was validated by PC tissue microarray. Function assay indicated that overexpression of FAM126A accelerates PC cell proliferation, invasion and migration in vitro, as well as liver cancer metastasis in vivo. Further, we found that FAM126A induces epithelial-mesenchymal transition (EMT), including the downregulation of E-cadherin epithelial marker expression, and the upregulation of N-cadherin, Vimentin, and Snail, mesenchymal marker expression. By co-localization and co-immunoprecipitation assays, we confirmed that FAM126A directly interacts with ENO1, which was a key activator of the PI3K/AKT signaling pathway. Furthermore, ENO1 knockdown reversed cell proliferation, migration, and invasion of PC cells promoted by FAM126A overexpression in vitro and in vivo. In general, these results verified FAM126A is an oncogene interacting with ENO1 in PC by activating PI3K/AKT signaling pathway.