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  3. Cancer testis antigen 55 deficiency attenuates colitis-associated colorectal cancer by inhibiting NF-κB signaling

Cancer testis antigen 55 deficiency attenuates colitis-associated colorectal cancer by inhibiting NF-κB signaling

  • Cell Death Dis. 2019 Apr 3;10(4):304. doi: 10.1038/s41419-019-1537-x.
Huan Zhao 1,  Wen-Ming Pan 2,  Hui-Hui Zhang 3,  Yang Song 1,  Jie Chen 1,  Ying Xiang 1,  Bo Gu 1,  Shang-Ze Li 4,  Run-Lei Du 1,  Xiao-Dong Zhang 5
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
  • 2 Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Laboratory of Molecular Biology, School of Medicine in Hunan Normal University, Changsha, Hunan, China.
  • 4 Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China. shangze.li@whu.edu.cn.
  • 5 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China. zhangxd@whu.edu.cn.
PMID: 30944312 DOI: 10.1038/s41419-019-1537-x
Abstract

Colitis-associated Cancer (CAC), a prototype of inflammation-associated Cancer, is one of the most common gastrointestinal tumors. As a potential Cancer testis antigen (CT antigen), Cancer testis antigen 55 (CT55) is expressed in different tumors and normal testes. However, its role in CAC remains unknown. Here, we identified CT55 as a new potent promoter of CAC. We discovered that Ct55 deficiency alleviated inflammatory responses, decreased cell proliferation and colitis-associated tumorigenesis in an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Mechanistically, CT55 acts as an accelerator of tumor necrosis factor (TNF)-α-induced nuclear factor-κB (NF-κB) signaling. Upon stimulation with TNF-α, CT55 interacts with the IκB kinase (IKK) complex, which increases the phosphorylation of IKKα/β and activates IKK-p65 signaling, while knockout of CT55 blocks IKK-p65 signaling. Notably, inhibition of IKK abolished the positive effect of CT55 on NF-κB activation. Collectively, our findings strongly indicate that CT55 deficiency suppresses the development of CAC and that the CT55-TNF-α-induced NF-κB axis may represent a promising target for CAC therapy.

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