Extracellular galectins as controllers of fibroblast growth factor receptor signaling
The ultimate goal of the project is to uncover the role of all galectin family members in the regulation of FGFRs trafficking and activity. We will determine which galectins interact with FGFRs and characterize in detail identified complexes. We will elucidate how galectins affect the interaction of FGFRs with other cellular proteins. Furthermore, presented studies will determine the role of galectins in the regulation of FGFR-mediated signaling and cellular transport. Last but not least, we will uncover how galectin-FGFRs cross-communication determines fate of the cells.
The expected results generated during the project implementation will be of high novelty and significance for the field. Decoding how these pivotal cellular proteins co-operate in the determination of the cell fate is of fundamental importance for cell and cancer biology. Furthermore, the results obtained in the frame of this project may facilitate the design of novel therapeutic strategies against cancers with aberrant galectins and FGF/FGFR signaling and give directions to the new targets and approaches in metabolic diseases, including diabetes.
Project carried out within the Sonata Bis-9 programme of the National Science Centre (2019/34/E/NZ3/00014)
Project duration: 2020-2025
Research Team:
Łukasz Opaliński (PhD, DSL) – project leader
Aleksandra Matynia (Msc)– PhD student
Dominika Żukowska (Msc)– PhD student
Natalia Porębska – PhD student
Marta Poźniak – PhD student
Paulina Gregorczyk – PhD student
Marta Kalka (PhD) – postdoc
Publications:
Żukowska D, Gędaj A, Porębska N, Poźniak M, Czyrek A, Krzyścik M, Krowarsch D, Otlewski J, Zakrzewska M, Opaliński Ł, Receptor clustering by a pecise set of extracellular galectins initiates FGFR signaling, Cellular and Molecular Life Sciences, 2023.
Gregorczyk P, Porębska N, Żukowska D, Chorążewska A, Gędaj A, Malinowska A, Otlewski J, Zakrzewska M, Opaliński Ł, N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope, Cell Communication and Signaling, 2023.
Gędaj A, Żukowska D, Porębska N, Poźniak M, Czyrek A, Krzyścik M, Krowarsch D, Otlewski J, Zakrzewska M, Opaliński Ł, Galectins use N-glycans of FGFs to capture growth factors in the extracellular matrix and fine-tune their signaling, Cell Communication and Signaling, 2023.
Pozniak M, Zukowska D, Gedaj A, Krzyscik M, Porebska N, Zakrzewska M, Otlewski J and Opaliński Ł, The significance of cell surface N-glycosylation for internalization and potency of cytotoxic conjugates targeting receptor tyrosine kinases, International Journal of Molecular Sciences, 2022.
Szymczyk J, Sochacka M, Chudy P, Opaliński Ł, Otlewski J, Zakrzewska M, FGF1 protects FGFR1-overexpressing cancer cells against taltobulin by activating AKT via two independent mechanisms, Frontiers in Oncology, 2022.
Krzyścik M, Opaliński Ł, Otlewski J, Cyclic and dimeric fibroblast growth factor 2 variants with high biomedical potential, International Journal of Biological Macromolecules, 2022.
Porębska N, Poźniak M, Matynia A, Żukowska D, Zakrzewska M, Otlewski J, Opaliński Ł, Galectins as modulators of receptor tyrosine kinases signaling in health and disease, Cytokines and Growth Factor Reviews, 2021.
Szymczyk J, Sluzalska KD, Materla I, Opaliński Ł, Otlewski J, Zakrzewska M, FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance, Cancers, 2021.
Porębska N, Knapik A, Poźniak M, Krzyścik M, Zakrzewska M, Otlewski J, Opaliński Ł, Intrinsically fluorescent oligomeric cytotoxic conjugate toxic for FGFR1 overproducing cancers, Biomacromolecules, 2021.