Activated Wnt signaling promotes growth and progression of AFP-producing gastric cancer in preclinical models

Cancer Management and Research
Dongshao ChenXiaotian Zhang

Abstract

Characterized by elevated AFP levels in serum, AFP-producing gastric cancer (APGC) is a very special type of gastric cancer (GC) that is difficult to treat and has poor prognosis. However, little is known about the role of AFP in GC, which was investigated in this study with in vitro and in vivo experiments. APGC cells were established with lentivirus infection and validated by PCR assay and ELISA in HCG27 and AGS cells. Cell growth, migration, and invasion were determined by CCK8, transwell assays, and animal experiments. RNA sequencing, Western blot, dual-luciferase-reporter assays, and RNA interference were employed to understand mechanisms underlying AFP activity, followed by therapeutic investigations for APGC. APGC cells featured significantly increased AFP levels in cellular supernatants. AFP potentiated growth and aggression in GC cell lines and their derived xenografts. Wnt-signaling activation was responsible for AFP function, indicated by decreased Axin 1 and pGSK3β, followed by cascade activation of β-catenin, downstream transcription factors TCF1/TCF7, and the target gene - c-Myc. Wnt-signaling blockade by Axin 1 rescue or pathway inhibitor XAV939 reversed AFP function, suggesting the potential therapeutic value of...Continue Reading

Citations

Jul 3, 2019·Cancers·Sara El-SahliSheng Liu

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Methods Mentioned

BETA
electrophoresis
ELISA
protein-assay
xenografts

Software Mentioned

SPSS

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