Where Ideas grow

Glycobiology in Cancer

ABOUT

The group “Glycobiology in Cancer” focus on the role that glycosylation plays in human cancer aiming at the understanding of the molecular mechanisms controlling alterations of glycosylation that are important in the process of carcinogenesis and cancer progression.

The main research projects are:

1) Characterization of the molecular mechanisms underlying the glycan-mediated adhesion of Helicobacter pylori and the understanding of the importance of the host-pathogen crosstalk for the chronic infection and gastric carcinogenesis.

2) Evaluation of the role of glycans and glycan-binding proteins in cancer and pre-cancerous conditions addressing the molecular mechanisms controlling glycosylation of key molecules involved in cancer development and progression, and identification of novel glycan-based biomarkers for clinical application.

The group applies multidisciplinary approaches combining molecular and cell biology, biochemistry, genomics, (glyco)proteomics and animal models for understanding and addressing key mechanisms and functions played by glycosylation in cancer.

 

RESEARCH

The group member’s main achievements include:

  • The understanding of how H. pylori modulates the host gastric mucosa glycophenotype and the evaluation of the impact of these glycosylation modifications on bacterial adhesion.  
  • The biological implications of glycosylation in H. pylori adhesion and infection using human clinical samples and genetically modified animal models.
  • The design of novel glycan-based therapeutic strategies for H pylori infection.
  • The characterization of the role of glycans and the glycosyltransferases controlling their biosynthesis in key cancer related molecules, such as E-cadherin, TKR and CEACAMs, providing novel biomarkers with clinical applications.
  • The characterization of glycosylation impact in the pathogenesis of pre-malignant conditions, such as inflammatory bowel disease.
  • The elucidation of the sialylated glycans biosynthesis and the role of glycan-binding proteins in cancer progression.

 

Glycosylation regulates key biological mechanisms in cancer cells.

Team Coordinators

Team

Selected Publications

Pinho S.S., Reis C.A.,
Glycosylation in cancer: Mechanisms and clinical implications. Nature Reviews Cancer15(9):540-555, 2015. [Journal: Review] [CI: 1001] [IF: 34,2]
DOI: 10.1038/nrc3982 SCOPUS: 84940449986. .

Mereiter S., Balmaña M., Campos D., Gomes J., Reis C.A.,
Glycosylation in the Era of Cancer-Targeted Therapy: Where Are We Heading?. Cancer Cell36(1):6-16, 2019. [Journal: Review] [CI: 57] [IF: 26,6]
DOI: 10.1016/j.ccell.2019.06.006 SCOPUS: 85067650826. .

Magalhães A., Duarte H.O., Reis C.A.,
Aberrant Glycosylation in Cancer: A Novel Molecular Mechanism Controlling Metastasis. Cancer Cell31(6):733-735, 2017. [Journal: Short Survey] [CI: 51] [IF: 22,8]
DOI: 10.1016/j.ccell.2017.05.012 SCOPUS: 85020642808. .

Marcos N.T., Pinho S., Grandela C., Cruz A., Samyn-Petit B., Harduin-Lepers A., Almeida R., Silva F., Morais V., Costa J., Kihlberg J., Clausen H., Reis C.A.,
Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer-associated Sialyl-Tn antigen. Cancer Research64(19):7050-7057, 2004. [Journal: Article] [CI: 146] [IF: 7,7]
DOI: 10.1158/0008-5472.CAN-04-1921 SCOPUS: 4944265751. .

Campos D., Freitas D., Gomes J., Magalhães A., Steentoft C., Gomes C., Vester-Christensen M.B., Ferreira J.A., Afonso L.P., Santos L.L., De Sousa J.P., Mandel U., Clausen H., Vakhrushev S.Y., Reis C.A.,
Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery. Molecular and Cellular Proteomics14(6):1616-1629, 2015. [Journal: Article] [CI: 54] [IF: 5,9]
DOI: 10.1074/mcp.M114.046862 SCOPUS: 84930470850. .

Carvalho S., Catarino T.A., Dias A.M., Kato M., Almeida A., Hessling B., Figueiredo J., Gartner F., Sanches J.M., Ruppert T., Miyoshi E., Pierce M., Carneiro F., Kolarich D., Seruca R., Yamaguchi Y., Taniguchi N., Reis C.A., Pinho S.S.,
Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer. Oncogene35(13):1619-1631, 2016. [Journal: Article] [CI: 59] [IF: 7,5]
DOI: 10.1038/onc.2015.225 SCOPUS: 84937605601. .

Marcos N.T., Magalhães A., Ferreira B., Oliveira M.J., Carvalho A.S., Mendes N., Gilmartin T., Head S.R., Figueiredo C., David L., Santos-Silva F., Reis C.A.,
Helicobacter pylori induces ß3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x. Journal of Clinical Investigation118(6):2325-2336, 2008. [Journal: Article] [CI: 89] [IF: 16,6]
DOI: 10.1172/JCI34324 SCOPUS: 45649085812. .

Zhang H., Freitas D., Kim H.S., Fabijanic K., Li Z., Chen H., Mark M.T., Molina H., Martin A.B., Bojmar L., Fang J., Rampersaud S., Hoshino A., Matei I., Kenific C.M., Nakajima M., Mutvei A.P., Sansone P., Buehring W., Wang H., Jimenez J.P., Cohen-Gould L., Paknejad N., Brendel M., Manova-Todorova K., Magalhães A., Ferreira J.A., Osório H., Silva A.M., Massey A., Cubillos-Ruiz J.R., Galletti G., Giannakakou P., Cuervo A.M., Blenis J., Schwartz R., Brady M.S., Peinado H., Bromberg J., Matsui H., Reis C.A., Lyden D.,
Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nature Cell Biology20(3):332-343, 2018. [Journal: Article] [CI: 344] [IF: 17,7]
DOI: 10.1038/s41556-018-0040-4 SCOPUS: 85042193942. .

Freitas D., Balmaña M., Poças J., Campos D., Osório H., Konstantinidi A., Vakhrushev S.Y., Magalhães A., Reis C.A.,
Different isolation approaches lead to diverse glycosylated extracellular vesicle populations. Journal of Extracellular Vesicles8(1):, 2019. [Journal: Article] [CI: 23] [IF: 15]
DOI: 10.1080/20013078.2019.1621131 SCOPUS: 85074725417. .

Gomes J., Mereiter S., Magalhães A., Reis C.A.,
Early GalNAc O-Glycosylation: Pushing the Tumor Boundaries. Cancer Cell32(5):544-545, 2017. [Journal: Short Survey] [CI: 5] [IF: 22,8]
DOI: 10.1016/j.ccell.2017.10.010 SCOPUS: 85033695819. .

Ongoing Projects

GastroCure .: GastroCure - Extratos bioativos de soja e vegetais crucíferos para aplicação em distúrbios gastrointestinais: desenvolvimento, caracterização e libertação
Reference: POCI-01-0145-FEDER-032094
Proponent: Ucatólica
Sponsor: FCT
From 01-JUL-18 to 30-JUN-21
GLYcanMATRIX .: Compreender a dinâmica dos glicanos das células de cancro e matriz extracelular como nova estratégia de intervenção na progressão tumoral
Reference: POCI-01-0145-FEDER-028489
Proponent: Ipatimup
Sponsor: FCT
From 26-JUL-18 to 25-JAN-22
GLYCOKiller .: Identificação de Novas Drogas Glicoespecíficos para Combater a Metástase de Células Cancerígenas
Reference: POCI-01-0145-FEDER-029780
Proponent: Ipatimup
Sponsor: FCT
From 01-JUL-18 to 30-JUN-22
GLYCANTIGENS .: Glicoantigénios da proteina MUC1: Um perspectiva estructural na luta contra o cancro
Reference: POCI-01-0145-FEDER-031028
Proponent: UNL
Sponsor: FCT
From 01-OCT-18 to 30-SEP-21
Nanopartículas Multifuncionais para Quimioradioterapia do Glioblastoma
Reference: POCI-01-0145-FEDER-029649
Proponent: IST
Sponsor: FCT
From 01-SEP-18 to 30-JUN-22
Combate aos cancros metastáticos: o palco é do ruténio.
Reference: NORTE-01-0145-FEDER-028662
Proponent: Faculdade de Ciências da Universidade de Lisboa
Sponsor: FCT
From 01-SEP-18 to 31-AUG-21
Passive immunotherapy against gastric cancer
Reference: CAR16
Proponent: Ipatimup
Sponsor: Umea University
From 01-APR-19 to 31-AUG-21
Novel CART targeting glycans for Cancer Immunotherapy
Reference: FBR_OC1_37
Proponent: Ipatimup
Sponsor: EEAGRANTS
From 16-JUN-20 to 28-FEB-22