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Sialyl-Lewis A (SLeA), a terminal glycoepitope of glycoproteins and glycolipids, offers tremendous potential towards this objective. It is rarely expressed in healthy tissues and blood cells, while it is present in highly metastatic cell lines and metastases. SLeA is also involved in E-selectin mediated metastasis, making it an ideal target to control disease dissemination. Methods and Results: To improve cancer specificity, we have explored the SLeA-glycoproteome of six GC cell models, with emphasis on glycoproteins showing affinity for E-selectin. A novel bioinformatics-assisted algorithm identified nucleolin (NCL), a nuclear protein, as a potential targetable biomarker potentially involved in metastasis. Several immunoassays, including Western blot and in situ proximity ligation reinforced the existence of cell surface NCL-SLeA glycoforms in GC. The NCL-SLeA glycophenotype was associated with decreased survival and was not reflected in relevant healthy tissues. Conclusions: NCL-SLeA is a biomarker of poor prognosis in GC holding potential for precise cancer targeting. This is the first report describing SLeA in preferentially nuclear protein, setting a new paradigm for cancer biomarkers discovery and targeted therapies.<\/jats:p>","DOI":"10.3390\/cancers12040861","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:57:14Z","timestamp":1585828634000},"page":"861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nucleolin-Sle A Glycoforms as E-Selectin Ligands and Potentially Targetable Biomarkers at the Cell Surface of Gastric Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-7432","authenticated-orcid":false,"given":"Elisabete","family":"Fernandes","sequence":"first","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Biomedical Engineering (INEB), Porto, Portugal, 4200-135 Porto, Portugal"},{"name":"Digestive Cancer Research Group, 1495-161 Alg\u00e9s, Portugal"}]},{"given":"Rui","family":"Freitas","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"}]},{"given":"Dylan","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Biomedical Engineering (INEB), Porto, Portugal, 4200-135 Porto, Portugal"},{"name":"Digestive Cancer Research Group, 1495-161 Alg\u00e9s, Portugal"}]},{"given":"Janine","family":"Soares","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"},{"name":"REQUIMTE-LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3015-9675","authenticated-orcid":false,"given":"Rita","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"}]},{"given":"Cristiana","family":"Gaiteiro","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"}]},{"given":"Andreia","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Biomedical Engineering (INEB), Porto, Portugal, 4200-135 Porto, Portugal"}]},{"given":"Sara","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"}]},{"given":"Sofia","family":"Cotton","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"}]},{"given":"Marta","family":"Relvas-Santos","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute for Biomedical Engineering (INEB), Porto, Portugal, 4200-135 Porto, Portugal"},{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Luis Pedro","family":"Afonso","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Pathology Department, Portuguese Institute of Oncology of Porto, 4200-162 Porto, Portugal"}]},{"given":"Carlos","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Immunology Department, Portuguese Institute of Oncology of Porto, 4200-162 Porto, Portugal"},{"name":"Health Science Faculty, University of Fernando Pessoa, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0272","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Biomedical Engineering (INEB), Porto, Portugal, 4200-135 Porto, Portugal"}]},{"given":"Rita","family":"Ferreira","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-7714","authenticated-orcid":false,"given":"Andr\u00e9 M. N.","family":"Silva","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, 4169-007 Porto, Portugal"}]},{"given":"L\u00facio","family":"Lara Santos","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"},{"name":"Digestive Cancer Research Group, 1495-161 Alg\u00e9s, Portugal"},{"name":"Health Science Faculty, University of Fernando Pessoa, 4249-004 Porto, Portugal"},{"name":"Department of Surgical Oncology, Portuguese Institute of Oncology of Porto, 4200-162 Porto, Portugal"},{"name":"Department, Porto Comprehensive Cancer Centre (P.ccc), 4200-162 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-6148","authenticated-orcid":false,"given":"Jos\u00e9 Alexandre","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, 4200-162 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-013 Porto, Portugal"},{"name":"Department, Porto Comprehensive Cancer Centre (P.ccc), 4200-162 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1158\/2159-8290.CD-11-0175","article-title":"Durable Complete Response of Metastatic Gastric Cancer with Anti-Met Therapy Followed by Resistance at Recurrence","volume":"1","author":"Catenacci","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00268-002-6279-7","article-title":"Incidence and Factors Associated with Recurrence Patterns after Intended Curative Surgery for Gastric Cancer","volume":"27","author":"Wu","year":"2003","journal-title":"World J. 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