A truncated form of IKKa is responsible for specific nuclear IKK activity in colorectal cancer
Author
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
Publication date
2012-10-25ISSN
2211-1247
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
616 - Pathology. Clinical medicine
Keywords
Còlon--Càncer
Metàstasi
Tumors
Oncologia
Cáncer de colon
Metástasis
Tumores
Oncología
Colon cancer
Metastasis
Tumors
Oncology
Pages
15
Publisher
Elsevier
Collection
2; 4
Is part of
Cell Reports
Citation
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.
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
© 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)
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/3.0/