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Expression and Role of Nuclear Receptor Coregulators in Colorectal Cancer Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri

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Expression and Role of Nuclear Receptor Coregulators in Colorectal Cancer Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri Expression and role of nuclear receptor coregulators in colorectal cancer Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri To cite this version: Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri. Expression and role of nuclear receptor coregulators in colorectal cancer. World Journal of Gastroenterology, Baishideng Publishing Group Co. Limited, 2017, 23 (25), pp.4480 - 4490. 10.3748/wjg.v23.i25.4480. inserm- 02438832 HAL Id: inserm-02438832 https://www.hal.inserm.fr/inserm-02438832 Submitted on 14 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Submit a Manuscript: http://www.f6publishing.com World J Gastroenterol 2017 July 7; 23(25): 4480-4490 DOI: 10.3748/wjg.v23.i25.4480 ISSN 1007-9327 (print) ISSN 2219-2840 (online) REVIEW Expression and role of nuclear receptor coregulators in colorectal cancer Mouna Triki, Marion Lapierre, Vincent Cavailles, Raja Mokdad-Gargouri Mouna Triki, Marion Lapierre, Vincent Cavailles, IRCM, Peer-review started: August 3, 2016 Institut de Recherche en Cancérologie de Montpellier, INSERM First decision: September 5, 2016 U1194, Université de Montpellier, Institut régional du Cancer de Revised: September 30, 2016 Montpellier, 34298 Montpellier, France Accepted: October 31, 2016 Article in press: October 31, 2016 Mouna Triki, Raja Mokdad-Gargouri, Centre de Biotechnologie Published online: July 7, 2017 de Sfax, Université de Sfax, Sfax 3072, Tunisie Author contributions: Triki M performed the literature review and analysis, wrote the manuscript and contributed to the generation of figures; Lapierre M and Mokdad-Gargouri R Abstract contributed to the drafting, editing and critical revision of the Colorectal cancer (CRC) is one of the most common manuscript; Cavailles V designed the aim of the review, generated human cancers and the cause of about 700000 deaths the figures and wrote the manuscript; all authors approved the final version. per year worldwide. Deregulation of the WNT/β-catenin pathway is a key event in CRC initiation. This pathway Supported by SIRIC and the PHC-UTIQUE program, No. interacts with other nuclear signaling pathways, 16G 0805; PHC-UTIQUE program, No. 16G 0805; Tunisian including members of the nuclear receptor superfamily government (Bourse d’alternance); INSERM, Université de and their transcription coregulators. In this review, Montpellier, INCa, SIRIC Montpellier, the Institut régional du we provide an overview of the literature dealing with Cancer de Montpellier. the main coactivators (NCoA-1 to 3, NCoA-6, PGC1-α, p300, CREBBP and MED1) and corepressors (N-CoR1 Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported. and 2, NRIP1 and MTA1) of nuclear receptors and summarize their links with the WNT/β-catenin signaling Open-Access: This article is an open-access article which was cascade, their expression in CRC and their role in selected by an in-house editor and fully peer-reviewed by external intestinal physiopathology. reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, Key words: Immunohistochemistry; Colon cancer; which permits others to distribute, remix, adapt, build upon this Nuclear receptors; Transcription coregulators; WNT work non-commercially, and license their derivative works on signaling different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. Manuscript source: Unsolicited manuscript Core tip: Colorectal cancer (CRC) is one of the most Correspondence to: Vincent Cavaillès, PhD, IRCM, Institut common human cancers worldwide. Deregulation of the de Recherche en Cancérologie de Montpellier, INSERM U1194, WNT/β-catenin pathway is a key event in CRC initiation. Université de Montpellier, Institut régional du Cancer de This pathway interacts with other nuclear signaling Montpellier, 208 rue des apothicaires, 34298 Montpellier, pathways, including members of the nuclear receptor France. [email protected] Telephone: +33-4-67612405 superfamily and their transcription coregulators. In Fax: +33-4-67613787 this review, we provide an overview of the literature dealing with the main coactivators and corepressors of Received: August 2, 2016 nuclear receptors, and summarize their links with the WJG|www.wjgnet.com 4480 July 7, 2017|Volume 23|Issue 25| Triki M et al . Nuclear receptor coregulators in CRC WNT/β-catenin signaling cascade, their expression in in CRC[9]. In normal intestinal cells, WNT expression is CRC and their role in intestinal physiopathology. detected in cells at the crypt base and is essential for the maintenance of stem cell compartmentalization and, ultimately, for the intestinal tract organization and Triki M, Lapierre M, Cavailles V, Mokdad-Gargouri R. patterning. The WNT canonical pathway is activated Expression and role of nuclear receptor coregulators in colorectal upon binding of the WNT ligands to the Frizzled/ cancer. World J Gastroenterol 2017; 23(25): 4480-4490 LRP receptor. This interaction induces a signaling Available from: URL: http://www.wjgnet.com/1007-9327/full/ cascade, leading to the stabilization of β­catenin v23/i25/4480.htm DOI: http://dx.doi.org/10.3748/wjg.v23. in the cytoplasm and to its translocation into the i25.4480 nucleus. There, β­catenin interacts with the TCF/LEF transcription factors to modulate specific target genes that are involved in cell proliferation and differentiation, INTRODUCTION such as MYC, which encodes the Myc proto­oncogene, and CCND1, which encodes the cyclin D1 protein. In Colorectal cancer the absence of WNT ligands, β­catenin is targeted for Colorectal cancer (CRC) is the third most common proteasomal degradation upon phosphorylation through human cancer with more than 1.3 million recorded its association with a destruction complex composed cases in 2012. Patients are generally treated with of various scaffold proteins, such as adenomatous surgery, chemotherapy and radiotherapy that are polyposis coli (APC), Axin 2, glycogen synthase kinase associated with several side effects. Despite important 3 (GSK3) and casein kinase 1 (CK1). Approximately advances in CRC prognosis, diagnosis and treatment 70%­80% of sporadic CRCs involve somatic mutations during the last decade, it remains the cause of about that inactivate APC, leading to β­catenin accumulation [1] 700000 deaths per year worldwide . Although CRC and activation of its target genes. can be sporadic or hereditary, in both cases, environ­ mental factors contribute to its development. The main Nuclear receptor signaling risk factor is age; however, diet, sedentary lifestyle and Nuclear receptors (NRs) are ligand­activated trans­ tobacco smoking also increase the risk of developing cription factors that directly regulate genes and are [2] CRC . involved in several physiological processes, such as CRCs are complex and heterogeneous epithelial growth, homeostasis, differentiation, development tumors that involve various genetic and epigenetic and metabolism[10]. NR signaling dysregulation contri­ alterations. The progressive accumulation of these butes to various human diseases, including cancer[11]. molecular changes contributes to the transformation Currently, NRs represent one of the largest families of [3] of normal mucosa into neoplasia . At least three transcription factors (48 members in humans) that can molecular pathways have been identified as involved be classified in three groups (hormone, metabolic and [4] in CRC pathogenesis . The most common is the orphan NRs), based on their ligand properties[10,12]. chromosomal instability (CIN) pathway, characterized Members of the hormone receptor subfamily generally by inactivation of tumor suppressor genes (APC, bind to DNA as homodimers and include estrogen [5] TP53, SMAD4) and activation of oncogenes (KRAS) . (ERα and ERβ), androgen (AR), progesterone (PR), The hallmark of the second molecular pathway is glucocorticoid (GR) and mineralocorticoid receptors microsatellite instability (MSI) that results from the (MR). Metabolic receptors, such as farnesoid X (FXR), deregulation of DNA mismatch repair (MMR) genes, liver X (LXR) and peroxisome proliferator­activated [6] leading to genetic hypermutability . Finally, the third receptors (PPARs), bind to DNA as heterodimers molecular mechanism involves gene silencing via with their obligate partner retinoid X receptor (RXR). aberrant hypermethylation of promoter CpG islands Orphan receptors include all NRs for which ligands [7] (CpG island methylator phenotype, or CIMP) . A recent were (or are still) unknown[10]. NRs share a modular study has proposed a unique molecular classification structure composed of an N­terminal activation of CRC based on gene expression with four consensus domain, which is important for interactions with core­ molecular subtypes (CMS): MSI immune (CMS1), gulators (activators and
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