The FOXM1/ATX signaling contributes to pancreatic cancer development

Dacheng Xie, Shijun Yu, Li Li, Ming Quan, Yong Gao
American Journal of Translational Research 2020, 12 (8): 4478-4487
Both autotaxin (ATX) and Forkhead Box M1 (FOXM1) have been commonly recognized as oncogenes in multiple types of human malignancies. However, the expression and biological functions of ATX in pancreatic ductal adenocarcinoma (PDAC), and its correlation with FOXM1 are poorly understood. The present study aimed to investigate their correlation and biological consequences in PDAC development. By dual luciferase reporter and chromatin immunoprecipitation assays, we found that ATX was a downstream transcriptional target gene of FOXM1. Further cellular functional experiments indicated that ATX was required for FOXM1-mediated PDAC cell proliferation and migration. Data from molecular biological experiments showed that ATX could enhance FOXM1 expression in turn by inhibiting the Hippo signaling pathway, suggesting that ATX and FOXM1 formed a positive feedback loop to facilitate PDAC progression. Using immunohistochemistry (IHC) method, both ATX and FOXM1 expression were found to be frequently up-regulated in PDAC tumor tissues when compared with adjacent normal tissues, and elevated ATX and FOXM1 expression were positively correlated with each other. In conclusion, the present work identified a positive feedback loop between ATX and FOXM1 which promotes PDAC cell proliferation and migration.

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