Phosphorylated alpha-enolase induces autoantibodies in HLA-DR8 pancreatic cancer patients and triggers HLA-DR8 restricted T-cell activation

Capello, Michela; Caorsi, Cristiana; Hernandez, Pablo Josè Bogantes; Dametto, Ennia; Bertinetto, Francesca; Mapelli, Paola; Rendine, S.; Amoroso, Antonio; Novelli, Francesco

doi:10.1016/j.imlet.2015.06.008

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…ENOA also known as Enolase 1 [ 15 ], is a metabolic enzyme that is implicated in pyruvate synthesis [ 87 ]. It facilitates the stimulation of extracellular matrix degradation and plasmin acting as a plasminogen receptor to promote tumour metastasis [ 87 , 88 ]. ENOA was elevated in in several malignancies, including breast, brain, gastric, cervix, colon, and kidney [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Althurwi

Beale

et al. 2020

IJMS

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In the present study, cisplatin, artemisinin, and oleanolic acid were evaluated alone, and in combination, on human ovarian A2780, A2780ZD0473R, and A2780cisR cancer cell lines, with the aim of overcoming cisplatin resistance and side effects. Cytotoxicity was assessed by MTT reduction assay. Combination index (CI) values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. Moreover, 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism, and biosynthetic processes and drug resistance and detoxification. Results indicate that appropriately sequenced combinations of cisplatin with artemisinin (ART) and oleanolic acid (OA) may provide a means to reduce side effects and circumvent platinum resistance.

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Section: Discussionmentioning

confidence: 99%

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Althurwi

Beale

et al. 2020

IJMS

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“…The expression levels of enolase may be different in different physiological, pathological, metabolic, developmental conditions of cells, [24] mitogenic stimuli in lymphocytes can increase the expression of ENOA, [25] similarly, hypoxia, production of inflammatory cytokines, bacterial lipopolysaccharide and other factors can also increase its expression. [26] The reason why ENOA was reduced in the colonic mucosa of IBS-D is unclear.…”

Section: Discussionmentioning

confidence: 99%

Close association between abnormal expressed enzymes of energy metabolism and diarrhea-predominant irritable bowel syndrome

Yao

Yang

2019

Chinese Medical Journal

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Background:Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls.Methods:Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test.Results:Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001).Conclusions:Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.

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“…The observed differences between the reactivity of EA-PCa and AA-PCa to ENO1 in different cell lines could be more consistent with a dependence on a specific ENO1 PTM profile for autoantibody recognition that is differentially present in metastatic PCa versus non-PCa cells. Precedent for this can be found on the previous observation that phosphorylation of ENO1 at serine 419 triggers autoantibody and T cell responses to this protein in genetically susceptible (HLA-DRB1-8ϩ) Italian patients with pancreatic cancer but not in control subjects (47,51,80). Our ENO1 PTM maps showed phosphorylation of this residue in ENO1 from PC3-DR cells (recognized by our selected EA-PCa sera but not by the selected AA-PCa sera), but this phosphorylation was not found in ENO1 PC3 (recognized by the EA-PCa and AA-PCa sera we tested, as well as the monoclonal antibody).…”

Section: Discussionmentioning

confidence: 99%

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins

Sanchez

Zhang

et al. 2016

Molecular & Cellular Proteomics

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African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities.

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Phosphorylated alpha-enolase induces autoantibodies in HLA-DR8 pancreatic cancer patients and triggers HLA-DR8 restricted T-cell activation

Cited by 15 publications

References 27 publications

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Close association between abnormal expressed enzymes of energy metabolism and diarrhea-predominant irritable bowel syndrome

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins

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