Double trouble: cytosolic and nuclear IKKα in cancer
IκB kinase alpha (IKKα) is a serine/threonine kinase originally known for its role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which integrates inflammatory processes and cancer. IKKα can function within the IKK complex in canonical NF-κB signalling, alongsi...
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| Language: | English |
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The Royal Society
2025-08-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.240375 |
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| author | Kirsty Tinto Margaret Cunningham Robin Plevin |
| author_facet | Kirsty Tinto Margaret Cunningham Robin Plevin |
| author_sort | Kirsty Tinto |
| collection | DOAJ |
| description | IκB kinase alpha (IKKα) is a serine/threonine kinase originally known for its role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which integrates inflammatory processes and cancer. IKKα can function within the IKK complex in canonical NF-κB signalling, alongside its homologous family member, IKKβ, and regulatory subunit IKKγ (NEMO). However, a key role for IKKα is its ability to promote non-canonical NF-κB signalling. Additionally, the dynamic ability of IKKα to shuttle between the cytosol and nucleus, mediates NF-κB-independent effects which further its role in inflammation and tumour progression. More recently, an endosomal-generated, nuclear-active IKKα isoform, p45-IKKα has been discovered and implicated in cancer and chemoresistance. This review focuses on current knowledge of the complex and intricate roles of nuclear and cytosolic IKKα in promoting tumour progression. By highlighting the molecular roles of IKKα in several cancer subtypes, and its integral roles in many of the hallmarks of cancer throughout this review, we highlight the therapeutic potential of IKKα as a future anti-cancer drug target. |
| format | Article |
| id | doaj-art-2fae6fb5eccb48ac99bbbf92db385e09 |
| institution | Kabale University |
| issn | 2046-2441 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj-art-2fae6fb5eccb48ac99bbbf92db385e092025-08-20T03:39:32ZengThe Royal SocietyOpen Biology2046-24412025-08-0115810.1098/rsob.240375Double trouble: cytosolic and nuclear IKKα in cancerKirsty Tinto0Margaret Cunningham1Robin Plevin2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UKIκB kinase alpha (IKKα) is a serine/threonine kinase originally known for its role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which integrates inflammatory processes and cancer. IKKα can function within the IKK complex in canonical NF-κB signalling, alongside its homologous family member, IKKβ, and regulatory subunit IKKγ (NEMO). However, a key role for IKKα is its ability to promote non-canonical NF-κB signalling. Additionally, the dynamic ability of IKKα to shuttle between the cytosol and nucleus, mediates NF-κB-independent effects which further its role in inflammation and tumour progression. More recently, an endosomal-generated, nuclear-active IKKα isoform, p45-IKKα has been discovered and implicated in cancer and chemoresistance. This review focuses on current knowledge of the complex and intricate roles of nuclear and cytosolic IKKα in promoting tumour progression. By highlighting the molecular roles of IKKα in several cancer subtypes, and its integral roles in many of the hallmarks of cancer throughout this review, we highlight the therapeutic potential of IKKα as a future anti-cancer drug target.https://royalsocietypublishing.org/doi/10.1098/rsob.240375cytosolicnuclearIKKαcancerNF-κB |
| spellingShingle | Kirsty Tinto Margaret Cunningham Robin Plevin Double trouble: cytosolic and nuclear IKKα in cancer Open Biology cytosolic nuclear IKKα cancer NF-κB |
| title | Double trouble: cytosolic and nuclear IKKα in cancer |
| title_full | Double trouble: cytosolic and nuclear IKKα in cancer |
| title_fullStr | Double trouble: cytosolic and nuclear IKKα in cancer |
| title_full_unstemmed | Double trouble: cytosolic and nuclear IKKα in cancer |
| title_short | Double trouble: cytosolic and nuclear IKKα in cancer |
| title_sort | double trouble cytosolic and nuclear ikkα in cancer |
| topic | cytosolic nuclear IKKα cancer NF-κB |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.240375 |
| work_keys_str_mv | AT kirstytinto doubletroublecytosolicandnuclearikkaincancer AT margaretcunningham doubletroublecytosolicandnuclearikkaincancer AT robinplevin doubletroublecytosolicandnuclearikkaincancer |