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.

Hyaluronic acid or hyaluronan is a biopolymer that accumulates in tumor microenvironments and around cancer cells. The accumulation is concomitant with changes of hyaluronan properties resulting in the generation of chains with different sizes. In this study, we mimic this peculiar tumor microenvironment and studied the response of gastric cancer cells. We selected two types of cells: AGS that have low expression of CD44 – a specific cellular receptor that recognize the hyaluronan and MKN45 with high CD44 expression.

Neste estudo foi possível identificar o papel de alterações de glicosilação específicas no comportamento de células de cancro gástrico e como estas contribuem para a progressão tumoral levando a um pior prognóstico dos pacientes. Era já conhecido que as células malignas apresentam alterações de expressão de glicanos com estrutura truncada. Nomeadamente, pacientes com cancro gástrico revelam ter um aumento de glicanos truncados, como por exemplo o Sialyl-Tn.

Authors and Affiliations:

Irene Gullo^1,2,3,4, Joana Carvalho^3,4, Diana Martins^3,4, Diana Lemos^3,4, Ana Rita Monteiro^3,4, Marta Ferreira^3,4, Kakoli Das⁵, Patrick Tan^5,6,7, Carla Oliveira^3,4, Fátima Carneiro^1,2,3,4, Patrícia Oliveira^3,4

¹ Department of Pathology, Centro Hospitalar de São João, Porto, Portugal

Authors and Affiliations:

Irene Gullo^1,2,3,4, Patrícia Oliveira^3,4, Maria Athelogou⁵, Gilza Gonçalves^2,3,4,6, Marta L Pinto^4,7,8, Joana Carvalho^3,4, Ana Valente^3,4, Hugo Pinheiro^3,4,9, Sara Andrade^3,4,10, Gabriela M. Almeida^3,4, Ralf Huss⁵, Kakoli Das¹¹, Patrick Tan^11,12,13, José C. Machado^2,3,4, Carla Oliveira^2,3,4, Fátima Carneiro^1,2,3,4

The most common cause of Hereditary Diffuse Gastric Cancer are germline mutations of the CDH1 gene. The vast majority of CDH1 germline alterations lead to truncated forms of E-cadherin with loss of protein function.

Authors and affiliations:

Gastric cancer is one of the most incident and deadly in the world. Helicobacter pylori infection plays a key role in the early stages of the process leading to the development of cancer. In this study, the authors show that there is a shift in the profile of the gastric microbiome from patients with chronic gastritis to patients with gastric cancer. The gastric microbiome of cancer patients is dysbiotic, presenting reduced microbial diversity, decreased abundance of H. pylori, and increased abundance of other species of bacteria.

Autores e Afiliações:

Henrique O. Duarte^1,2,3, Meritxell Balmaña^1,2, Stefan Mereiter^1,2, Hugo Osório^1,2,4, Joana Gomes^1,2 and Celso A. Reis^1,2,3,4

¹Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal

²Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal

Cell surface receptor tyrosine kinases (RTKs) play a central role in the initiation, promotion and progression of multiple human cancers, by triggering the aberrant activation of downstream signaling pathways implicated in malignant cell phenotype and behavior. In particular, overexpression of the human epidermal growth factor 2 (ErbB2) RTK constitutes a well-established molecular driver of carcinogenesis. RTK maturation is tightly regulated by protein N-linked glycosylation.