Article ; Online: Critical and distinct roles of cell type-specific NF-κB2 in lung cancer.
JCI insight
2024 Volume 9, Issue 4
Abstract: Different from the well-studied canonical NF-κB member RelA, the role of the noncanonical NF-κB member NF-κB2 in solid tumors, and lung cancer in particular, is poorly understood. Here we report that in contrast to the tumor-promoting role of RelA, NF- ... ...
| Abstract | Different from the well-studied canonical NF-κB member RelA, the role of the noncanonical NF-κB member NF-κB2 in solid tumors, and lung cancer in particular, is poorly understood. Here we report that in contrast to the tumor-promoting role of RelA, NF-κB2 intrinsic to lung epithelial and tumor cells had no marked effect on lung tumorigenesis and progression. On the other hand, NF-κB2 limited dendritic cell number and activation in the lung but protected lung macrophages and drove them to promote lung cancer through controlling activation of noncanonical and canonical NF-κB, respectively. NF-κB2 was also required for B cell maintenance and T cell activation. The antitumor activity of lymphocyte NF-κB2 was dominated by the protumor function of myeloid NF-κB2; thus, NF-κB2 has an overall tumor-promoting activity. These studies reveal a cell type-dependent role for NF-κB2 in lung cancer and help understand the complexity of NF-κB action and lung cancer pathogenesis for better design of NF-κB-targeted therapy against this deadliest cancer. |
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| MeSH term(s) | Humans ; NF-kappa B/metabolism ; NF-kappa B p52 Subunit ; Lung Neoplasms |
| Chemical Substances | NF-kappa B ; NF-kappa B p52 Subunit |
| Language | English |
| Publishing date | 2024-02-22 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.164188 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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