Maintenance of tissue homeostasis depends on complex intercellular growth factor signaling networks that govern many basic cell functions.  Therefore, alterations in growth factor signalling networks are prerequisites for cancer development. The fibroblast growth factor family (FGF) and their high affinity cell-surface receptors (FGFR) represent one of the fundamental signaling networks governing cell communication. Imbalances in FGF signaling are known to induce/promote all hallmarks of cancer that malignant cells must acquire.
We want to understand in details the mechanisms how FGF/FGFR generate specific signaling outputs in diverse biological context and how such signaling is regulated in normal and cancer cells. It will result in better understanding of the biology of tumor induction and progression of malignancy as well as new opportunities to develop specific targeted therapies for cancer.

Contact information:
Email: antoni.wiedlocha@ous-research.no
Department of Molecular Cell Biology, Institute for Cancer Research
The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway
Phone +47 22 78 19 30 (Wiedlocha), Switchboard: +47 22 93 40 00

Kostas M, Haugsten EM, Zhen Y, Sørensen V, Szybowska P, Fiorito E, Lorenz S, Jones N, de Souza GA, Wiedlocha A, Wesche J (2018)
Protein Tyrosine Phosphatase Receptor Type G (PTPRG) Controls Fibroblast Growth Factor Receptor (FGFR) 1 Activity and Influences Sensitivity to FGFR Kinase Inhibitors
Mol Cell Proteomics, 17 (5), 850-870
DOI 10.1074/mcp.RA117.000538, PubMed 29371290

Mateusz Adam Krzyscik, Malgorzata Zakrzewska, Vigdis Sørensen, Aleksandra Sokolowska-Wedzina, Michal Lobocki, Karolina Weronika Swiderska, Daniel Krowarsch, Antoni Wiedlocha, and Jacek Otlewski (2017)
Cytotoxic Conjugates of Fibroblast Growth Factor 2 (FGF2) with Monomethyl Auristatin E for Effective Killing of Cells Expressing FGF Receptors
ACS Omega, 2017, 2 (7), pp 3792–3805 Publication Date (Web): July 21, 2017 (Article)
DOI: 10.1021/acsomega.7b00116

Wendel T, Zhen Y, Suo Z, Bruheim S, Wiedlocha A (2016)
The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo
Exp Cell Res, 340 (2), 220-6
PubMed 26748184

Sletten T, Kostas M, Bober J, Sorensen V, Yadollahi M, Olsnes S, Tomala J, Otlewski J, Zakrzewska M, Wiedlocha A (2014)
Nucleolin regulates phosphorylation and nuclear export of fibroblast growth factor 1 (FGF1).
PLoS One. 2014 Mar 4;9(3)e90687.
Pubmed 24595027

Nadratowska-Wesolowska B, Haugsten EM, Zakrzewska M, Jakimowicz P, Zhen Y, Pajdzik D, Wesche J, Wiedlocha A (2014)
RSK2 regulates endocytosis of FGF receptor 1 by phosphorylation on serine 789.
Oncogene. 2014 Oct. 40, 4823-36
Pubmed 24141780

Zakrzewska M, Haugsten EM, Nadratowska-Wesolowska B, Oppelt A, Hausott B, Jin Y, Otlewski J, Wesche J, Wiedlocha A (2013)
ERK-Mediated Phosphorylation of Fibroblast Growth Factor Receptor 1 on Ser777 Inhibits Signaling.
Sci Signal. 6(262)
23405013  Free pdf

Jin Y, Zhen Y, Haugsten EM, Wiedlocha A (2011)
The driver of malignancy in KG-1a leukemic cells, FGFR1OP2-FGFR1, encodes an HSP90 addicted oncoprotein
Cell Signal. 11;1758-66
Pubmed 21745565.

Project title: Highly cytotoxic FGF2-conjugates in targeted therapy for FGFR-expressing cancers.

This project is funded from Norway Grants in the Polish-Norwegian Research Programme operated by the National Centre for Research and Development.