gastric cancer

Researchers from the "Differentiation and Cancer" group at i3S, in collaboration with “Cancer Metastasis” and “Cell Division & Genomic Stability” groups and Carmen Jerónimo from IPO-Porto, elucidated the role of YTHDF3, a key m6A RNA “reader” protein, as a driver of gastric cancer (GC) progression and paclitaxel sensitivity. This new study, entitled "The RNA‑binding protein YTHDF3 affects gastric cancer cell migration and response to paclitaxel by regulating EZRIN," was recently published in the journal "Gastric Cancer”.

Researchers from the "Differentiation and Cancer" group at i3S, in collaboration with António Pombinho, from the "BioSciences Screening" platform, and Filipe Pereira, from Lund University, elucidated the role of the transcription factor HMGA1 in gastric cancer stem cells. The study, entitled "HMGA1 stimulates cancer stem-like features and sensitivity to monensin in gastric cancer," was recently published in the journal "Experimental Cell Research."

The i3S Epithelial Interactions in Cancer group coordinated a multidisciplinary team to address how germline alterations of E-cadherin trigger different clinical manifestations. The group was intrigued by the fact that loss of E-cadherin function may cause hereditary diffuse gastric cancer (HDGC) and congenital malformations, such as orofacial clefts (OFC).

Researchers from the Differentiation and Cancer group at i3S investigated the expression of the MISP protein and its clinical relevance in gastric cancer. The study, titled "MISP Is Overexpressed in Intestinal Metaplasia and Gastric Cancer," was recently published in the journal Current Oncology. Gastric cancer remains a major health problem worldwide, so the identification of new biomarkers and therapeutic targets is imperative.

Gastric cancer remains one of the most incident and deadly worldwide. It is usually detected in more advanced stages and therefore, the available treatments are not always sufficient to treat patients, leading to a low survival rate. Additionally, in some cases after an apparently successful treatment the cancer recurs. The recognition of cancer stem cells (CSCs) as keys of the tumorigenic process, metastasis and resistance to radio- and chemotherapy makes them an essential target for an efficient cancer treatment.

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