Functional relationship of colorectal cancer-associated glycans with malignant phenotype and transcriptome changes

Gomes Ferreira, Ines Isabel (2019) Functional relationship of colorectal cancer-associated glycans with malignant phenotype and transcriptome changes, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia, ematologia e patologia, 31 Ciclo. DOI 10.6092/unibo/amsdottorato/8874.
Documenti full-text disponibili:
[img] Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (6MB)

Abstract

Glycosyltransferases ST6GAL1 and B4GALNT2 (and their cognate antigens Sia6LacNAc and Sda, respectively) are associated with colorectal cancer (CRC) but it is not fully clear their biological and clinical significance. We explored the clinical relevance of both glycosyltransferases by interrogating The Cancer Genome Atlas (TCGA) database while the phenotypic/transcriptomic effects of ST6GAL1/B4GALNT2 overexpression were studied in genetically modified CRC cell lines. Transcriptomic data from CRC patients in TCGA database suggested a moderate impact of ST6GAL1 on CRC progression, although it was not possible to define a clear role for this glycosyltransferase. Transcriptomic analysis of ST6GAL1-transduced cell lines revealed a much deeper effect of ST6GAL1 on gene expression in SW948 than in SW48. The overexpression of ST6GAL1 induced opposite effects on soft agar growth and wound healing in both cell lines. These results indicate that the impact of a cancer-associated glycosyltransferase change on phenotype/transcriptome can be extremely variable, depending on the molecular context of the tumor cell. On the contrary, transcriptomic analysis of B4GALNT2-modified cell lines together with TCGA database survey demonstrated a strong impact of B4GALNT2 on the transcriptional activity of CRC cells, in particular its association with a better prognosis. We suggest an anti-tumoral role of B4GALNT2 in CRC. We also investigated the glycan changes related to ST6GAL1/B4GALNT2 expression in a small cohort of tissues/plasma as well as the N-glycomic profile of CRC, normal and polyp tissues. We found an increase of ST6GAL1 activity in CRC and inflammatory bowel disease plasma samples comparing with plasma from healthy donors. A different Sda protein carrier pattern was observed between healthy donors and CRC plasma samples. β-arrestin 1 is a possible candidate as Sda carrier protein in plasma samples although future validation studies are needed. The alterations found in the N-glycan pattern highlight the importance of N-glycome as a molecular signature in cancer.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Gomes Ferreira, Ines Isabel
Supervisore
Dottorato di ricerca
Ciclo
31
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
glycosylation, colorectal cancer, glycosyltransferase, ST6GAL1, B4GALNT2
URN:NBN
DOI
10.6092/unibo/amsdottorato/8874
Data di discussione
12 Aprile 2019
URI

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi

^