| First Author | Rajamanickam V | Year | 2020 |
| Journal | Int J Biol Sci | Volume | 16 |
| Issue | 8 | Pages | 1288-1302 |
| PubMed ID | 32210720 | Mgi Jnum | J:303144 |
| Mgi Id | MGI:6511395 | Doi | 10.7150/ijbs.39098 |
| Citation | Rajamanickam V, et al. (2020) Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis. Int J Biol Sci 16(8):1288-1302 |
| abstractText | Toll-like receptor (TLR) signaling is an emerging pathway in tumor cell invasion and metastasis. Myeloid differentiation protein-2 (MD2) contributes to ligand recognition and activation of TLRs in response to exogenous microbial insults or endogenous agents. We hypothesized that blocking MD2 using a specific inhibitor would prevent TLR4-mediated inflammatory responses and metastatic cancer growth. Here, we report that a MD2 inhibitor, L6H21, inhibited migration and invasion of LPS-activated colon cancer CT26.WT cells. These activities were accompanied by inhibition of nuclear factor-kappaB (NF-kappaB) activation, and thereby inhibition of the production of pro-inflammatory cytokines and adhesive molecules in colon cancer cells. Furthermore, L6H21 inhibited CT26.WT metastasis to the lung in BALB/c mice as well as suppressed colitis-induced colon cancer induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Taken together, our results demonstrated that L6H21 suppressed tumor invasion and metastasis through blocking TLR4-MD2/NF-kappaB signaling axis. These findings reveal that inhibition of MD2 may be an important target for the development of colon cancer therapies. |
