Altered glycosylation in cancer: dissecting the molecular mechanisms and understanding the clinical implications
Celso A. Reis, i3S - Institute for Research and Innovation in Health, University of Porto
Host: Angelina S. Palma, UCIBIO NOVA
ZOOM link: https://bit.ly/GuestSeminarsUCIBIO
ID da reunião: 865 7786 0516
Abstract: Alterations of glycosylation are common molecular alterations with major biological implications for cancer progression. Cancer is a heterogeneous disease that requires multidisciplinary treatment. Current targeted therapy depends on patient stratification based on molecular features of the tumor. This presentation will report on the basis of alterations of glycosylation that occur in cancer. Recent results applying glycomic and glycoproteomic strategies in human cancer that provided novel information with major clinical implications. This presentation will report on the alterations of glycosylation impact the activation of oncogenic receptors in tumour samples, such as RON, MET, EGFR and HER2 (ErbB2). I will also report on the glycoproteomic map of the HER2 in gastric cancer cells which disclosed a site-specific glycosylation profile of this receptor in gastric cancer cells and how this HER2 glycosylation affects the biology of the receptor and the sensitivity of HER2-dependent gastric cancer cells to the therapeutic humanized monoclonal antibody trastuzumab.
These results highlight the functional aspects of glycosylation modifications occurring in cancer and supports their potential application as biomarkers for patient stratification, personalize medicine and for novel and improved therapeutic applications.
Short CV: Celso A. Reis is the Head of the Glycobiology in Cancer group at i3S - Institute for Research and Innovation in Health, University of Porto, where he leads an international multidisciplinary team working on the Glycobiology in human diseases with focus on Cancer. ORCID: https://orcid.org/0000-0002-0286-6639
Celso A. Reis has published 220 peer-reviewed papers as well as several patents, with over 13400 citations and with H-index of 55 (Scopus). His research focus on the role of glycosylation in human cancer. He has addressed the molecular mechanisms controlling glycosylation in cancer cell biology, more specifically the role of glycosyltransferases regulating the biosynthesis of glycans in cancer. These included the role of sialyltransferases leading to the biosynthesis of terminal sialylated glycan antigens expressed by cancer cells. He also contributed for seminal studies determining the role of these glycosylation modifications and the consequences to cancer cell biology, including the mechanisms regulating cancer invasion, metastasis and tumour glycoimmunology. Celso A. Reis has also contributed to the application of glycoconjugates as biomarkers in human cancer and pre-neoplastic lesions, and the application of novel unique therapeutic strategies. Currently, he develops novel strategies to improve cancer diagnosis prognosis and to improve cancer treatment based on glycans that can be used as markers for cancer patient stratification, as well as glycans and glycoconjugates that can be used as novel targets in advanced cancer therapy strategies.