GADD34 Promotes Tumor Growth by Inducing Myeloid-derived Suppressor Cells
Liu, L.; Ito, S.; Nishio, N.; Sun, Y.; Tanaka, Y.; Isobe, K-Ichi.
Anticancer Research 36(9): 4623-4628
2016
ISSN/ISBN: 0250-7005 PMID: 27630304 Document Number: 688510
Tumor hypoxia induces the expression of growth arrest and DNA damage-inducible protein (GADD34). However, the role of GADD34 in tumor growth remains unclear. Gadd34 expression was knocked-down through lentivirus-mediated short hairpin RNA (shRNA) in tumor cells, which were subsequently injected subcutaneously into mice. Tumor volumes and myeloid-derived suppressor cells (MDSCs) were monitored. Isolated MDSCs were incubated with tumor supernatant to investigate the impact of GADD34 on cytokine secretion of MDSCs. We observed that reduction of GADD34 expression significantly suppressed tumor, and resulted in decreased accumulation of MDSCs and T-cells, and inhibition of GADD34 reduced secretion of vascular epithelial growth factor α and transforming growth factor β by MDSCs. These findings provide a promising strategy for targeting GADD34 activity in order to inhibit tumor growth.