Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2018; 24(48): 5454-5461
Published online Dec 28, 2018. doi: 10.3748/wjg.v24.i48.5454
Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer: An update
Rafael I Jaén, Patricia Prieto, Marta Casado, Paloma Martín-Sanz, Lisardo Boscá
Rafael I Jaén, Patricia Prieto, Lisardo Boscá, Department of Metabolism and Physiopathology of Inflammatory Diseases, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid 28029, Spain
Marta Casado, Department of Biomedicine, Instituto de Biomedicina de Valencia (CSIC), Valencia 46010, Spain
Marta Casado, Paloma Martín-Sanz, Lisardo Boscá, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, y Hepáticas y Digestivas, ISCIII, Madrid 28029, Spain
Paloma Martín-Sanz, Lisardo Boscá, Unidad Asociada IIBM-ULPGC, Universidad de las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria 35001, Spain
Author contributions: Jaén RI and Prieto P contributed equally to the discussion of the minireview and provided key information on the glycosylation of prostaglandin-endoperoxide synthase 2 in colorectal cancer samples. Casado M, Martín-Sanz P and Boscá L revised the literature, organized the content of the minireview and prepared the figures of the manuscript.
Supported by Ministerio de Ciencia Innovación y Universidades, No. SAF2017-82436R and SAF2016-75004R; Comunidad de Madrid, No. S2017/BMD-3686; Fundación Ramón Areces, No. 2016/CIVP18A3864; and Instituto de Salud Carlos III and by Fondos FEDER, No. Cibercv and Ciberehd.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Lisardo Boscá, BM, BCh, PhD, Senior Research Fellow, Department of Metabolism and Physiopathology of Inflammatory Diseases, Instituto de Investigaciones Biomédicas Alberto Sols, Arturo Duperier 4, Madrid 28029, Spain.
Telephone: +34-91-4972747 Fax: +34-91-4972747
Received: October 7, 2018
Peer-review started: October 7, 2018
First decision: November 7, 2018
Revised: November 13, 2018
Accepted: November 13, 2018
Article in press: November 16, 2018
Published online: December 28, 2018

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specific microRNAs to proteins that control mRNA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the pro-inflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

Keywords: Prostaglandins, Prostaglandin-endoperoxide synthase 2, Post-translational modifications, Glycosylation, Colorectal cancer, Inflammation

Core tip: The post-translational modifications of prostaglandin-endoperoxide synthase 2 (PTGS2) appear to be specific signatures of this enzyme in human colorectal cancer (CRC). Glycosylations of PTGS2 that alter the electrophoretic mobility of the protein are mainly observed in the tumor samples but are absent in the non-tumor samples obtained from these patients. These modifications not only may play a pathophysiological role in the progression of CRC but also may provide new biomarkers to develop specific therapeutic interventions.