Abstract 3533: Connections between NF-κB misregulation and carcinogenesis

In this review poster, we researched the function, regulation, and structure of NF-κB as it relates to carcinogenesis. Found in almost all animal cells, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor that plays various roles in cellular proliferation, cell survival, inflammation, and T cell activation. There are two different NF-κB signaling pathways: the canonical pathway and the non-canonical pathway. NF-κB forms a p50/Rel A heterodimer in the canonical pathway and a p52/ Rel B heterodimer in the non-canonical pathway. NF-κB protein is normally sequestered in the cytoplasm as an inactive complex with a κB inhibitor (IκB) protein. Outside stimuli such as reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) activate cell surface receptors such as Toll-Like Receptors (TLRs) and Receptor Activators of NF-κB (RANK). These surface receptors, in turn, activate IκB kinase (IKK). IKK phosphorylates IκB, which causes ubiquitination of IκB, signaling proteasomes to degrade it. NF-κB then enters the nucleus through a nuclear pore and forms a transcription complex with coactivators and RNA polymerase. NF-κB binds to specific DNA-binding sites to induce transcription. One of the target genes of NF-κB encodes IκBs, so NF-κB regulates its own activity through a negative feedback loop. Because the cell maintains storage of the signaling protein NF-κB in the cytoplasm, NF-κB allows the cell to respond to sudden stimuli by activating quick changes in gene expression. Because proteins that promote cellular proliferation and cell survival are mainly transcribed through NF-κB activation, uncontrolled overactivation of this transcription factor has major implications in carcinogenesis. Many types of cancer cells have high levels of constitutively active NF-κB. Mutations in the genes for NF-κB itself or its inhibitors such as IκBs often found in cancer cells can cause cells to accelerate their proliferation or confer resistance to apoptosis. Some types of cancer cells secrete signaling molecules, inducing improper NF-κB activity. Because of the tumor promoting characteristics of NF-κB activation, a focus of current research is to find methods of suppressing NF-κB to kill cancer cells or slow their growth. We designed a 3D-printed model of the p50/RelA NF-κB protein using Jmol to highlight the relationship between its structure and function. Citation Format: Donian I. Chyong, Aurian Naderi, Chase Lee, Ty Arpornsuksant, Allison Lu, Megha Dilip, Margaret Zhang, Young-Joon Surh, Eun-Ji Lee, Hye-Kyung Na. Connections between NF-κB misregulation and carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2017-3533