RT Journal Article
SR Electronic
T1 Maelstrom Directs Myeloid-Derived Suppressor Cells to Promote Esophageal Squamous Cell Carcinoma Progression via Activation of the Akt1/RelA/IL8 Signaling Pathway
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 1246
OP 1259
DO 10.1158/2326-6066.CIR-17-0415
VO 6
IS 10
A1 Li, Pupu
A1 Chen, Xinfeng
A1 Qin, Guohui
A1 Yue, Dongli
A1 Zhang, Zhen
A1 Ping, Yu
A1 Wang, Dan
A1 Zhao, Xuan
A1 Song, Mengjia
A1 Zhao, Qitai
A1 Li, Jieyao
A1 Liu, Shasha
A1 Wang, Dong
A1 Zhang, Chaoqi
A1 Lian, Jingyao
A1 Cao, Ling
A1 Li, Feng
A1 Huang, Lan
A1 Wang, Liping
A1 Yang, Li
A1 Huang, Jianmin
A1 Li, Hong
A1 Zhang, Bin
A1 Zhang, Yi
YR 2018
UL http://cancerimmunolres.aacrjournals.org/content/6/10/1246.abstract
AB Maelstrom (MAEL) is a novel cancer/testis-associated gene, which is not only expressed in the male testicular germ cells among human normal tissues, but is also aberrantly expressed in various cancer tissues. In our study, MAEL was characterized as a tumor-promoting gene and was significantly associated with esophageal squamous cell carcinoma (ESCC) recurrence and unfavorable prognosis. Kaplan–Meier analysis showed that patients with high MAEL expression had a shorter survival time. Functional experiments showed that MAEL promoted tumor cell growth and inhibited cell apoptosis. These results prompted us to investigate the factors affecting the tumorigenicity of MAEL. Further experimentation demonstrated that MAEL enhanced the expression of phosphorylated Akt1, with subsequent phosphorylation of nuclear factor kappa B (NF-κB) subunit RelA in tumor cells, and chemoattracted myeloid-derived suppressor cells (MDSCs) by upregulating interleukin-8 (IL8) to accelerate tumor progression in the tumor microenvironment. We also found that TGFβ secreted by MDSCs could upregulate MAEL by inducing Smad2/Smad3 phosphorylation. In summary, this study revealed a mechanism by which MAEL could upregulate IL8 through Akt1/RelA to direct MDSCs homing into the tumor, suggesting that MAEL could be an attractive therapeutic target and a prognostic marker against ESCC. Cancer Immunol Res; 6(10); 1246–59. ©2018 AACR.