Targeting Frizzled-7 Decreases Stemness and Chemotherapeutic Resistance in Gastric Cancer Cells by Suppressing Myc Expression
Yongzhong Cheng, Li Li, Sirong Pan, Huilin Jiang, Hongyan Jin
Department of Oncology, Wuhan Puren Hospital, Wuhan, Hubei, China (mainland)
Med Sci Monit 2019; 25:8637-8644
Although the promoting roles of Frizzled-7 (Fzd7) have been shown before, its effects in gastric cancer (GC) cell stemness are still unclear. The present study assessed the effects of Fzd7 on GC cell stemness and chemoresistance.
MATERIAL AND METHODS: Clinical samples were used to detect Fzd7 expression and online datasets were used to analyze the correlation between Fzd7 expression and GC patient prognosis. Quantitative real-time PCR (qPCR), Western blot, and spheroid formation were used to detect the stemness of cells and Fzd7-mediated effects on GC cell stemness. Cell viability was assessed to evaluate the role of Fzd7 in chemoresistance of GC cells.
RESULTS: We found that the expression of Frizzled-7 (Fzd7), a Wnt receptor, was increased in gastric cancer (GC) cells and tissues. Additionally, Fzd7 expression was correlated with shorter overall survival of GC patients. Knockdown of Fzd7 or using inhibitors of Wnt/Fzd (OMP-18R5/Vantictumad) decreased GC cell stemness, characterized as a decrease of spheroid formation ability and expression of stemness regulators. Notably, Fzd7 knockdown or inhibitors of Wnt/Fzd attenuated the chemoresistance of GC cells. Furthermore, elevation of Myc expression rescued the effects of Fzd7 inhibition on GC cell stemness and chemoresistance.
CONCLUSIONS: Our results suggest that inhibition of Fzd7 decreases the stemness and chemotherapeutic resistance of GC cells.
Keywords: Neoplastic Stem Cells, Stomach Neoplasms, Wnt Signaling Pathway