| First Author | Zhang S | Year | 2022 |
| Journal | Biochem Biophys Res Commun | Volume | 621 |
| Pages | 46-52 | PubMed ID | 35810590 |
| Mgi Jnum | J:328323 | Mgi Id | MGI:7326789 |
| Doi | 10.1016/j.bbrc.2022.07.004 | Citation | Zhang S, et al. (2022) Deletion of IKKbeta in activated fibroblasts promotes tumor progression in melanoma. Biochem Biophys Res Commun 621:46-52 |
| abstractText | Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and play critical roles in tumorigenesis. CAFs consists of multiple subpopulations, which have diverse functions. The detailed mechanism, including the role of NF-kappaB, a critical transcription factor for inflammation and cell survival, in CAFs has not been adequately explored. In this study, we examined the roles of IKKbeta, a key kinase for NF-kappaB activation, in activated CAFs by using mice (KO mice) with deletion of IKKbeta in activated fibroblasts (aFbs). We found that melanoma cells implanted in KO mice showed significantly more growth than those implanted in control mice. To exclude the effects of deletion of IKKbeta in cells other than aFbs, we implanted a mixture of melanoma cells and IKKbeta-deleted aFbs in wild-type mice and observed that the mixture showed greater growth than a mixture of melanoma cells and normal aFbs. In exploring the mechanisms, we found that conditioned medium from IKKbeta-deleted aFbs promotes the proliferation of melanoma cells, and the expression of growth arrest-specific 6 (GAS6) and hepatocyte growth factor (HGF), which are major tumor-promoting factors, was upregulated in IKKbeta-deleted aFbs. These results indicated the tumor-suppressing function of IKKbeta in activated CAFs. |
