Maelstrom directs myeloid-derived suppressor cells to promote esophageal squamous cell carcinoma progression via activation of the Akt1/RelA/IL8 signaling pathway

Pupu Li, Xinfeng Chen, Guohui Qin, Dongli Yue, Zhen Zhang, Yu Ping, Dan Wang, Xuan Zhao, Mengjia Song, Qitai Zhao, Jieyao Li, Shasha Liu, Dong Wang, Chaoqi Zhang, Jingyao Lian, Ling Cao, Feng Li, Lan Huang, Liping Wang, Li YangJianmin Huang, Hong Li, Bin Zhang, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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-kB) 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 TGFb 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.

Original languageEnglish (US)
Pages (from-to)1246-1259
Number of pages14
JournalCancer Immunology Research
Volume6
Issue number10
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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