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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 | Model of angiogenesis in mice with severe combined immunodeficiency (SCID)and xenoengrafted with Epstein-Barr virus transformed B cells显示文摘 | Call D R Remick D g | 2004 | Comp Med2004，54，2： | 1 |
| 3 | Silver toxicity to #Chironomus# tentans in two freshwater sediments显示文摘 | CALL D J POLKINGHORNE C N MARKEE T P | 1999 | Environmental Toxicological Chemistry1999，18，1： | 1 |
| 4 | Dopaminergic modulation of neuropathic pain: Analgesia in rats bya D2-type receptor agonist 显示文摘 | Cobacho N de la Calle JL Paino CL | 2014 | Brain Res Bull2014，106，： | 1 |
| 5 | Removal of naphthalene,phenanthrene,and pyrene by sorbents from hot gas显示文摘 | MASTRAL A M GARCIAA T CALLEN M S | 2001 | Environ Sci Technol2001，35，： | 1 |
| 6 | Pollination effects on fruit and seed development in Comice pear显示文摘 | Call N W | 1978 | J Amer Soc Hort Sci1978，103，4： | 1 |
| 7 | Three-ring PAH removal from waste hot gas by sorbents:influence of the sorbent characteristics显示文摘 | MASTRAL A M GARCIAA T CALLEN M S | 2002 | Environ Sci Technol2002，36，： | 1 |
| 8 | The ocular ischemic syndrome 显示文摘 | Foncea Beti N Mateo I Diaz La Calle V | 2003 | Clin Neurol Neurosurg2003，106，1： | 1 |
| 9 | A novel role of the hedgehog pathway in lens regeneration显示文摘 | Tsonis P A Vergara M N Spence J R Madhavan M Kramer E L Call M K | 2004 | Dev Biol2004，267，： | 1 |
| 10 | The ocular ischemic syndrome显示文摘 | Foncea Beti N Mateo I Diaz La Calle V | 2003 | Clin Neurol Neurosurg2003，106，： | 1 |
| 11 | A Methodfor Thermal Characterization and Modeling of Large Gantry-type MachineTools显示文摘 | Gomez-Acedo E Olarra A Lopez de la Calle L N | 2012 | Internation- al Journal of Advanced Manufacturing Technology2012，62，912： | 1 |
| 12 | Assessment of PAH emissions as a function of coal combustion variables显示文摘 | Ana María Mastral Marisol Callén Ramón Murillo | 1996 | Fuel1996，，： | 1 |
| 13 | Bort- ezom ibresistant nuclear fact or - kappa B activity in multiple myeloma cells 显示文摘 | Mark ovina S Call ander N S O'Connor S L | 2008 | Mol Cancer Res2008，6，8： | 1 |
| 14 | A new algorithm for initial cluster centers in k-means algorithm 显示文摘 | Erisoglu M Calls N Sakallioglu S | 2011 | Pattern Recognition Letters2011，32，14： | 1 |
| 15 | Adorption ofphenanthrene on activated carbons: breakthrough curve modeling 显示文摘 | Murillo R Garc?a T Aylón E Callén M S | 2004 | Carbon2004，42，： | 1 |
| 16 | 439 I148M PNPLA3 VARIANT PROMOTES STEATOSIS ACCORDING TO VIRAL AND IL28B GENOTYPE BUT DOES NOT AFFECT SUSTAINED VIRAL RESPONSE IN PATIENTS WITH HEPATITIS C显示文摘 | J. Ampuero L. Rojas R. Calle L. Ortíz-Fernández J.R. García- Lozano R. Solá X. Forns R. Andrade M. Diago J.A. Pons J.M. Navarro R. Millán M. González-Escribano M. Romero- Gómez | 2013 | Journal of Hepatology2013，，： | 1 |
| 17 | Characterisation and source attribution of the semi-volatile organic content of atmospheric particles and associated vapour phase in Birmingham, UK显示文摘 | Harrad S Hassoun S Calle' n Romero M S Harrison R M | 2003 | Atmospheric Environment2003，37，： | 1 |
| 18 | Imng in vasenar disease显示文摘 | Khan N Me Call J | 2007 | Surgery2007，25，8： | 1 |
| 19 | The ocular ischemic syndrome显示文摘 | Foncea Beti N Mateo I Diaz La Calle V | 2003 | Clin Neurol Neurosurg2003，106，1： | 1 |
| 20 | A review on polycyclic aromatic hydrocarbon (PAH) emissions from energy generation 显示文摘 | Mastral A M Callén M S | 2000 | Environmental Science and Technology2000，34，15： | 1 |
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