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

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)-?-induced nuclear factor-?B (NF-?B) signaling. Upon stimulation with TNF-?, CT55 interacts with the I?B kinase (IKK) complex, which increases the phosphorylation of IKK?/? 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-?B activation. Collectively, our findings strongly indicate that CT55 deficiency suppresses the development of CAC and that the CT55-TNF-?-induced NF-?B axis may represent a promising target for CAC therapy.

SUBMITTER: Zhao H

PROVIDER: S-EPMC6447546 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Zhao Huan H Pan Wen-Ming WM Zhang Hui-Hui HH Song Yang Y Chen Jie J Xiang Ying Y Gu Bo B Li Shang-Ze SZ Du Run-Lei RL Zhang Xiao-Dong XD

Cell death & disease 20190403 4

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 tumorigenesi ...[more]

PMID: 30944312

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Dataset Information

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

Publications

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

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