| First Author | Zhao H | Year | 2019 |
| Journal | Cell Death Dis | Volume | 10 |
| Issue | 4 | Pages | 304 |
| PubMed ID | 30944312 | Mgi Jnum | J:280149 |
| Mgi Id | MGI:6369257 | Doi | 10.1038/s41419-019-1537-x |
| Citation | Zhao H, et al. (2019) Cancer testis antigen 55 deficiency attenuates colitis-associated colorectal cancer by inhibiting NF-kappaB signaling. Cell Death Dis 10(4):304 |
| abstractText | 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)-alpha-induced nuclear factor-kappaB (NF-kappaB) signaling. Upon stimulation with TNF-alpha, CT55 interacts with the IkappaB kinase (IKK) complex, which increases the phosphorylation of IKKalpha/beta 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-kappaB activation. Collectively, our findings strongly indicate that CT55 deficiency suppresses the development of CAC and that the CT55-TNF-alpha-induced NF-kappaB axis may represent a promising target for CAC therapy. |
