A truncated form of IKKa is responsible for specific nuclear IKK activity in colorectal cancer
Autor/a
Margalef, Pol
Fernández-Majada, Vanessa
Villanueva, Alberto
Garcia-Carbonell, Ricard
Iglesias, Mar
López, Laura
Martínez-Iniesta, María
Mulero, Mari Carmen
Andreu, Montserrat
Torres, Ferran
Mayo, Marty W.
Bigas, Anna
Espinosa, Lluis
Fecha de publicación
2012-10-25ISSN
2211-1247
Resumen
Nuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis and IKKα activity remains poorly understood. We have now analyzed 288 human colorectal cancer samples and found a significant association between the presence of nuclear IKK and malignancy. Importantly, the nucleus of tumor cells contains an active IKKα isoform with a predicted molecular weight of 45 kDa (p45-IKKα) that includes the kinase domain but lacks several regulatory regions. Active nuclear p45-IKKα forms a complex with nonactive IKKα and NEMO that mediates phosphorylation of SMRT and histone H3. Proteolytic cleavage of FL-IKKα into p45-IKKα is required for preventing the apoptosis of CRC cells in vitro and sustaining tumor growth in vivo. Our findings identify a potentially druggable target for treating patients with advance refractory CRC.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
61 - Medicina
616 - Patología. Medicina clínica. Oncología
Palabras clave
Còlon--Càncer
Metàstasi
Tumors
Oncologia
Cáncer de colon
Metástasis
Tumores
Oncología
Colon cancer
Metastasis
Tumors
Oncology
Páginas
15
Publicado por
Elsevier
Colección
2; 4
Publicado en
Cell Reports
Citación
Margalef, Pol; Fernández-Majada, Vanessa; Villanueva, Alberto [et al.]. A truncated form of IKKa is responsible for specific nuclear IKK activity in colorectal cancer. Cell Reports, 2012, 2(4), p. 840-854. Disponible en: <https://www.sciencedirect.com/science/article/pii/S2211124712002689?via%3Dihub>. Fecha de acceso: 28 oct. 2020. DOI: 10.1016/j.celrep.2012.08.028.
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Derechos
© 2012 The Authors. Published by Elsevier Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License (CC-BY-NC-ND; http://creativecommons.org/licenses/by-nc-nd/3.0/ legalcode)
Excepto si se señala otra cosa, la licencia del ítem se describe como https://creativecommons.org/licenses/by-nc-nd/3.0/