title: Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics.
abstract: Glycosylation is the most frequent and structurally complex posttranslational modification in cell-surface and secreted proteins. Glycans are major orchestrators of biological processes, namely, by controlling protein folding and key biological functions such as cell adhesion, migration, signaling and immune recognition. Altered glycosylation is considered a hallmark of malignant transformations that decisively contributes to disease outcome. This review comprehensively summarizes the main findings related with gastrointestinal cancers and the decisive impact of aberrant glycosylation on tumor biology toward more aggressive phenotypes. Particular emphasis is given to alterations in O-glycosylation, namely, the overexpression of immature O-glycans, and the sialylated Lewis antigens sialyl-LeA and sialyl-LeX, frequently implicated in lymphohematogenous metastasis. We further discuss how recent contributions from glycoproteomics and glycoengineering fields have broadened our understanding of the human O-glycoproteome and its implications for cancer research. Finally, we address the tremendous potential of glycans in the context of targeted therapeutics (selective inhibition of glycosylation pathways, immunotherapy) and discuss the need to include glycomics/glycoproteomics in holistic panomics models toward true precision medicine settings.
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313, Porto, Portugal. Electronic address: jose.a.ferreira@ipoporto.min-saude.pt.
authors.forename: José Alexandre
authors.initials: JA
authors.lastname: Ferreira
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Peixoto
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Gaiteiro
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Fernandes
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal; Health School of University of Fernando Pessoa, 4249-004, Porto, Portugal; Department of Surgical Oncology, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072, Porto, Portugal.
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313, Porto, Portugal; Faculty of Medicine of the University of Porto, 4200-319, Porto, Portugal.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy
chemical_list: D006023:Glycoproteins; D009363:Neoplasm Proteins; D011134:Polysaccharides
keywords: Cancer glycans; Colorectal cancer; Gastric cancer; Glycoprotomics; Protein glycosylation; Targeted therapeutics