Uncovering the funtions of FGF homologous factors – FHFs

Understanding of proteins function is one of the fundamental task of contemporary bioscience, allowing for diagnosis and therapy of various diseases. The project focuses on revealing of the molecular role of FHFs (FGF homologous factors), proteins group belonging to the family of fibroblast growth factors (FGFs). FHFs are considered as intracellular molecules that are not involved in signal transduction. They have been shown to be important as regulators of ion channels in nervous and cardiac tissues, however, in contrast to other FGFs, their functions in other cell types have not been yet discovered. Our preliminary data indicate, for the first time, that FHFs may act outside the cell, being able to activate FGF receptor, initiate signal transduction and protect the cell against apoptosis. Therefore, within the project we will study various aspects of FHFs biology and the role of these proteins in different locations. The planned research includes a wide, multidisciplinary approaches such as genetic engineering, proteomics techniques, protein-protein interaction measurements and advanced methods of cell biology and microscopy. Thanks to them, we will thoroughly characterize cellular functions of FHFs and largely expand the knowledge on biology of FHF proteins. The results of project will contribute to the better understanding of the molecular mechanisms of FHFs action, facilitating the design of novel therapeutic strategies.

Project carried out within the OPUS 16 Programme of National Science Centre (2018/31/B/NZ3/01656)

Project duration: 2019-2022

Research team:

Małgorzata Zakrzewska (PhD) – project leader

Łukasz Opaliński (PhD)

Daniel Krowarsch (PhD)

Martyna Sochacka (MSc) – PhD student

Martyna Biaduń (MSc) – PhD student

Radosław Karelus (MSc) – PhD student

Papers:

1. Pozniak M, Sokolowska-Wedzina A, Jastrzebski K, Szymczyk J, Porebska N, Krzyscik M, Zakrzewska M, Miaczynska M, Otlewski J, Opalinski L. FGFR1 clustering with engineered tetravalent antibody improves the efficiency and modifies the mechanism of receptor internalization Mol Oncol. 2020;14:1998–2021. doi: 10.1002/1878-0261.12740

2. Sochacka M, Opalinski L, Szymczyk J, Zimoch M, Czyrek A, Krowarsch D, Otlewski J, Zakrzewska M. FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner. Cell Commun Signal. 2020;18(1):69. doi: 10.1186/s12964-020-00573-2

3. 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. Cytokine Growth Factor Rev. 2021 Aug;60:89-106. doi: 10.1016/j.cytogfr.2021.03.004.

4. Poźniak M, Porębska N, Krzyścik MA, Sokołowska-Wędzina A, Jastrzębski K, Sochacka M, Szymczyk J, Zakrzewska M, Otlewski J, Opaliński Ł. The cytotoxic conjugate of highly internalizing tetravalent antibody for targeting FGFR1-overproducing cancer cells.Mol Med. 2021 May 7;27(1):46. doi: 10.1186/s10020-021-00306-2.

5. Sochacka M, Karelus R, Opalinski L, Krowarsch D, Biadun M, Otlewski
J, Zakrzewska M. FGF12 is a novel component of the nucleolar NOLC1/TCOF1
ribosome biogenesis complex. Cell Commun Signal. 2022 Nov 21;20(1):182.
doi: 10.1186/s12964-022-01000-4.