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| 1 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 2 | Determinants of Release Rate of Tetanus Vaccine from Polyester Microspheres显示文摘 | ALONSO M J COHEN S PARK T G | 1993 | Pharm Res1993，10，： | 1 |
| 3 | Complex event detection at wire speed with FPGAs 显示文摘 | WOODS L TEUBNER J ALONSO G | 2010 | Proceedings of the VLDB Endowment2010，3，12： | 1 |
| 4 | Gout and risk of Parkinson disease: a prospective study显示文摘 | Alonso A Rodriguez L A Logroscino G | 2007 | Neurology2007，69，17： | 1 |
| 5 | Quantitative study of fluvial landscapes:Case study in Madrid, Spain显示文摘 | Castil o V. S Antonio D Alonso S. G | | 0，，1： | 1 |
| 6 | Database replication:a tale of research across communities显示文摘 | KEMME B ALONSO G | 2010 | Proceedings of the VLDB endowment2010，3，12： | 1 |
| 7 | Heat transfer studies inan inorganic membrane reactor at pilot plant s(-ale显示文摘 | Alonso M Patience G Fernandez J R | 2006 | CatalysisToday2006，118，12： | 1 |
| 8 | Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression显示文摘 | ALONSO R GRIEBEL G PAVONE G | 2004 | Mol Psychiatry2004，9，22： | 1 |
| 9 | Repeated morphine treatment alters pelysialylated neural cell adhesion molecule, glutamate decarboxylase- 67 expression and cell proliferation in the adult rat hippocampus显示文摘 | Kahn L Alonso G Normand E | 2005 | Eur J Neurosci2005，21，2： | 1 |
| 10 | Preparation of MoS2 and WS2 catalysts by in situ decomposition of ammonium thiosalts显示文摘 | Alonso G Del Valle M Cruz J Petranovskii V LiceaClaverie A Fuentes S | | 0，，： | 1 |
| 11 | Physicochemical Transformations of Coal Particles During Pyrolysis and Combustion显示文摘 | Alonso M J G Borrego A G Alvarez D | 2001 | Fuel2001，80，13： | 1 |
| 12 | Multiplicity of solutions for elliptic problems with critical exponent or with a nonsymmetric term显示文摘 | AZORERO J P G ALONSO I P | 1991 | Tram Amer Math Soc1991，323，2： | 1 |
| 13 | Light and excess manganese implications for oxidative stress in common bean显示文摘 | Alonso G | 1998 | Plant Physiol1998，118，： | 1 |
| 14 | Baseline of butyltin pollution in coastal sediments within the Basque Country (northern Spain), in 2007-2008显示文摘 | Rodriguez J G~ Solaun O Larreta J Segarra M J B Franco J Alonso J I G Sariego C Valencia V Borja A | 2010 | Marine Pollution Bulletin2010，60，1： | 1 |
| 15 | A rapid design process for total care product creation 显示文摘 | ALONSO R T THOMPSON G | 2006 | Journal of Engineering Design2006，17，6： | 1 |
| 16 | EIN2, a bifunctional transducer of ethylene and stress responses in Arabidopsis 显示文摘 | ALONSO J M HIRAYAMA T ROMAN G | 1999 | Science1999，284，5423： | 1 |
| 17 | Screening of substrate analogs as potential enzyme inhibitors for the argi nine kinase of Trypanosoma cruzi显示文摘 | PEREIRA C A ALONSO G D IVAUDI S | 2003 | Journal of Eukaryotic Microbiology2003，50，2： | 1 |
| 18 | Graphene for toughand electroconductive alumina ceramics 显示文摘 | CENTENO A ROCHA V G ALONSO B | 2013 | J Eur Ceram Soc2013，33，32： | 1 |
| 19 | Contraction stress and physical properties development of a resin- based composite irradiated using modulated curing meth- ods at two C-factor levels 显示文摘 | Cunha L G Alonso R C Pfeifer C S | 2008 | Dent Mater2008，24，3： | 1 |
| 20 | Reactivity of highly cycled particles of CaO in a carbonation/calcination loop显示文摘 | Grasa G S Abanades J C Alonso M | 2008 | Chemical Engineering Journal2008，137，3： | 1 |
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