Research project objectives

The DC3 research project will focus on the evaluation of glycosyltransferases inhibitors and targeted approaches in gastrointestinal cancer models.

1) Analysis of the effects of the selected inhibitors in the glycan biosynthesis mediated by the targeted glycosyltransferases using glycoengineered cancer cell models.
2) Characterization and monitoring of the glycomic and glycoproteomic features induced by the inhibitors in advanced cancer models,
3) Evaluation of the functional biological effect of the glycosyltransferases inhibitors in cancer cells.
4) Analysis of the glycan-based therapeutic efficacy on the cancer models.

Instituto de Investigação e Inovação em Saúde (i3S)

The host laboratories (i3S) are equipped with modern equipment and facilities for analysis of the functional effects in the tumour biology and their potential therapeutic applications. Cell culture, molecular and genetic engineering, protein biochemistry, flow cytometry and FACS, confocal and electron microscopy, HPLCs, Mass (ESI/MS) spectrometers, proteomics, high-throughput screening and animal model facilities. Full access to the literature databases.

Selected papers (10):

  1. Mereiter S., Balmaña M., Campos D., Gomes J., Reis C.A. Glycosylation in the Era of Cancer-Targeted Therapy: Where Are We Heading?. Cancer Cell 36(1):6-16, 2019. DOI: 10.1016/j.ccell.2019.06.006
  2. Duarte H.O., Rodrigues J.G., Gomes C., Hensbergen P.J., Ederveen A.L.H., de Ru A.H., Mereiter S., Polónia A., Fernandes E., Ferreira J.A., van Veelen P.A., Santos L.L., Wuhrer M., Gomes J., Reis C.A. ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab. Oncogene 40(21):3719-3733, 2021. DOI: 10.1038/s41388-021-01801-w
  3. Rodrigues J.G., Duarte H.O., Gomes C., Balmaña M., Martins Á.M., Hensbergen P.J., de Ru A.H., Lima J., Albergaria A., van Veelen P.A., Wuhrer M., Gomes J., Reis C.A. Terminal a2,6-sialylation of epidermal growth factor receptor modulates antibody therapy response of colorectal cancer cells. Cellular Oncology 44(4):835-850, 2021. DOI: 10.1007/s13402-021-00606-z
  4. Costa A.F., Campos D., Reis C.A., Gomes C. Targeting Glycosylation: A New Road for Cancer Drug Discovery. Trends in Cancer 6(9):757-766, 2020. DOI: 10.1016/j.trecan.2020.04.002
  5. 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 Research 64(19):7050-7057, 2004. DOI: 10.1158/0008-5472.CAN-04-1921
  6. Freitas D., Campos D., Gomes J., Pinto F., Macedo J.A., Matos R., Mereiter S., Pinto M.T., Polónia A., Gartner F., Magalhães A., Reis C.A. O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype. EBioMedicine 40:349-362, 2019. DOI: 10.1016/j.ebiom.2019.01.017
  7. Poças J., Marques C., Gomes C., Otake A.H., Pinto F., Ferreira M., Silva T., Faria-Ramos I., Matos R., Ribeiro A.R., Senra E., Cavadas B., Batista S., Maia J., Macedo J.A., Lima L., Afonso L.P., Ferreira J.A., Santos L.L., Polónia A., Osório H., Belting M., Reis C.A. Costa-Silva B., Magalhães A. Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival. Proceedings of the National Academy of Sciences of the United States of America 120(20):, 2023. DOI: 10.1073/pnas.2214853120
  8. Martins Á.M., Lopes T.M., Diniz F., Pires J., Osório H., Pinto F., Freitas D., Reis C.A. Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization. Advanced Science:, 2023. DOI: 10.1002/advs.202300588
  9. 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 Proteomics 14(6):1616-1629, 2015. DOI: 10.1074/mcp.M114.046862
  10. Pinho S.S., Reis C.A Glycosylation in cancer: Mechanisms and clinical implications. Nature Reviews Cancer 15(9):540-555, 2015. DOI: 10.1038/nrc3982