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Deciphering the influence of CD276 glycode in colorectal cancer immunomodulation

2025-09-19Dissertação de mestrado Acesso embargado
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dc.contributor.advisorPeixoto, Andreia
dc.contributor.advisorFerreira, José Alexandre
dc.contributor.advisorSantos, Lúcio Lara
dc.contributor.advisorFerraz, Ricardo
dc.contributor.authorMagalhães, Mariana Moura
dc.date.accessioned2026-02-25T13:49:54Z
dc.date.available2026-02-25T13:49:54Z
dc.date.issued2025-09-19
dc.description.abstractColorectal cancer (CRC) remains a major contributor to cancer-related illness and death worlwide, with aggressive subtypes often resistant to conventional therapies. The imune checkpoint protein CD276 (B7-H3) is highly expressed in CRC and is associated with poor prognosis, tumor progression, and imune evasion. CD276 undergoes extensive glycosylation, a modification that influences protein stability, localisation, and imune interactions, yet the specific roles of its glycosylation in CRC are not well understood. This study examines how immature 0-glycosylation of CD276 affects CRC aggressiveness. To model the altered glycan landscape typical of cancer cells, C1GALT1-knockout CRC cells, which lack the enzyme necessary for 0-glycan elongation, were used. The effects of CD276 knockdown using small interfering RNA (siRNA) on cell proliferation and inasion were assessed by BrdU ELISA and Matrigel invasion assays, respectivily. Additionally, proteomic and phisphoproteomic analyses were conducted to explore how CD276 influences oncogenic signalling pathways. Our fundings reveal that aberrant, immature 0-glycosylation of CD276 promotes CRC cell proliferation and invasion by sustaining oncogenic biosynthetic and phosphorylation networks. Conversely, CD276 depletion activates stress responses involving RNA processing. DNA repair, and mitochondrial reorganisation, highlighting CD276 as a glycosylation-dependent driver of CRC aggressiveness and a potential therapuetic target.eng
dc.description.sponsorship2022.08311 CEECIND 2023.06366 CEECIND CI-IPOP-29-2014 CI-IPOP-58-2015
dc.identifier.tid204180066
dc.identifier.urihttp://hdl.handle.net/10400.22/31911
dc.language.isoeng
dc.rights.uriN/A
dc.subjectColorectal cancer
dc.subjectCD276
dc.subject0-glycosylation
dc.subjectImune checkpoint
dc.titleDeciphering the influence of CD276 glycode in colorectal cancer immunomodulationeng
dc.typemaster thesis
dspace.entity.typePublication
thesis.degree.nameMestre em Bioquímica em Saúde-Bioquímica Clínica e Metabólica

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ESS - DM - Bioquímica em Saúde