Celso A. Reis

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O-glycan truncation enhances cancer-related functions of CD44 in gastric cancer

CD44 isoforms are often upregulated in gastric cancer and have been associated with increased metastatic potential and poor survival. To evaluate the functional impact of O-glycan truncation on CD44 we have analysed glycoengineered cancer cell models displaying shortened O-glycans. Here, we demonstrate that induction of aberrant O-glycan termination through various molecular mechanisms affects CD44 molecular features.

A glicosilação do CD44 na regulação da sua função no cancro gástrico

Os glicanos são estruturas polissacarídeas ligadas a proteínas ou lípidos que modificam as propriedades bioquímicas destas macromoléculas a nível estrutural e funcional. Em diversas patologias, perturbações nas vias de biosíntese da glicosilação podem levar à expressão de glicanos aberrantes, alterando funções de diversas proteínas. No cancro, estas estruturas podem conferir fenótipos agressivos como, por exemplo, invasão e migração.

Multicellular Human Gastric Cancer Spheroids Mimic the Glycosylation Phenotype of Gastric Carcinomas

3-dimensional (3D) systems mimic better the in vivo features of the tumor, however, the in vitro studies of cancer have been traditionally performed using 2D methods. In this study, published in the journal Molecules, a high-throughput 3D methodology has been established for four different gastric cancer cell lines. These cancer models have been fully characterised, focusing on the glycosylation profile, since it is known that changes in glycosylation are key players in cancer development and progression.

Novos modelos 3D para melhor simular a glicosilação dos tumores

Sistemas tridimensionais (3D) reproduzem melhor as características in vivo do tumor, no entanto, os estudos in vitro do cancro têm sido tradicionalmente realizados usando métodos 2D. Neste estudo, publicado na revista Molecules, uma metodologia 3D de alta produtividade foi estabelecida para quatro diferentes linhas celulares de cancro gástrico. Esses modelos de cancro foram totalmente caracterizados, focando-se no perfil de glicosilação, uma vez que está descrito que modificações na glicosilação são alterações-chave no desenvolvimento e progressão do cancro.

Early GalNAc O-Glycosylation: Pushing the Tumor Boundaries

Cellular glycosylation occurring during cancer development and progression represent key features of tumor cell malignant behavior. In this publication, the authors preview and discuss the findings of Nguyen et al. (Cancer Cell. 2017 Nov 13;32(5):639-653) who identified a molecular mechanism in which the relocation of a glycosyltransferase mediating protein O-glycosylation initiation, from the Golgi to endoplasmic reticulum, leads to aberrant glycosylation.

Early GalNAc O-Glycosylation: Pushing the Tumor Boundaries

Cellular glycosylation occurring during cancer development and progression represent key features of tumor cell malignant behavior. In this publication, the authors preview and discuss the findings of Nguyen et al. (Cancer Cell. 2017 Nov 13;32(5):639-653) who identified a molecular mechanism in which the relocation of a glycosyltransferase mediating protein O-glycosylation initiation, from the Golgi to endoplasmic reticulum, leads to aberrant glycosylation.

Aberrant Glycosylation in Cancer: A Novel Molecular Mechanism Controlling Metastasis – PREVIEW

Major alterations in cell glycosylation occurring during cancer development and progression represent key features of tumor cell malignant behavior. In this publication, the authors preview and put in context the findings of Agrawal et al. (Cancer Cell, Vol. 31, Issue 6, 2017) that identified and characterized a novel molecular mechanism in which aberrant glycosylation actively tunes the metastatic capacity of melanoma cells by preventing the proteolytic cleavage of the L1CAM adhesion molecule.

 

Authors and Affiliations:

Aberrant Glycosylation in Cancer: A Novel Molecular Mechanism Controlling Metastasis – PREVIEW

Major alterations in cell glycosylation occurring during cancer development and progression represent key features of tumor cell malignant behavior. In this publication, the authors preview and put in context the findings of Agrawal et al. (Cancer Cell, Vol. 31, Issue 6, 2017) that identified and characterized a novel molecular mechanism in which aberrant glycosylation actively tunes the metastatic capacity of melanoma cells by preventing the proteolytic cleavage of the L1CAM adhesion molecule.

 

Autores e Afiliações:

Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer

Authors and Affiliations:

Stefan Mereiter a,b,c, Ana Magalhães a,b, Barbara Adamczyk d, Chunsheng Jin d, Andreia Almeida e,f, Lylia Drici g,Maria Ibáñez-Vea g, Catarina Gomes a,b, José A. Ferreira a,b,h, Luis P. Afonso i, Lúcio L. Santos h,j, Martin R. Larsen g, Daniel Kolarich e, Niclas G. Karlsson d, Celso A. Reis a,b,c,k

a i3S — Instituto de Investigação e Inovação em Saúde, University of Porto, Portugal

b Institute of Molecular Pathology and Immunology of the University of Porto — IPATIMUP, Porto, Portugal

Alterações de glicosilação: um novo mecanismo de ativação de vias oncogénicas

A expressão de antigénios sialilados, como o silayl Lewis X (SLeX), está associada a tumores mais agressivos com pior prognóstico. Neste estudo, publicado na revista Biochimica et Biophysica Acta, foi utilizada uma linha celular gástrica com sobre expressão de uma enzima envolvida na biossíntese do antigénio SLeX, a glicosiltransferase ST3GalIV. Foram avaliadas a nível estrutural as alterações do perfil de O- e N-glicosilação deste modelo celular e foi possível identificar 47 proteínas com um aumento significativo de N-glicanos sialilados.