Metastasis is responsible for more than 80% of cancer-associated deaths, yet the mechanism of dissemination is still poorly understood. Therapy failure eventually leads to metastasis, which is usually refractory to treatment. One major developmental process hijacked by cancer cells for metastatic spreading and treatment escape is the epithelial to mesenchymal transition (EMT), which is the initial step of the metastatic cascade, associated with the acquisition of cancer stem cell properties and resistance to anticancer therapies.
Interleukin-like EMT inducer (ILEI), also called FAM3C, is one of the secreted factors that regulate tumor progression. Increased secretion and altered subcellular localization of ILEI is associated with unfavorable prognosis.
Using cellular and mouse model systems of EMT and tumor progression, our aim is to understand the molecular mechanisms of ILEI function and regulation in cancer pathogenesis as well as its contribution to drug tolerance and resistance.
- Evaluation of Interleukin-like-EMT-inducer (ILEI) as a prognostic marker and therapeutic target in carcinomas (Marle Poppelaars)
- Analysis of pathways sustaining drug tolerance using organoid-based breast cancer models (Sai Nagender Sama)
- Molecular characterization of drug-tolerant persister cells to overcome chemotherapy induced relapse in breast cancer (Silvia Steinbauer)
The FAM3C locus that encodes interleukin-like EMT inducer (ILEI) is frequently co-amplified in MET-amplified cancers and contributes to invasiveness
Schmidt U, Heller G, Timelthaler G, Heffeter P, Somodi Z, Schweifer N, Sibilia M, Berger W, Csiszar A*
J Exp Clin Cancer Res. 2021 Feb 17;40(1):69. doi: 10.1186/s13046-021-01862-5.
Covalent dimerization of interleukin-like epithelial-to-mesenchymal transition (EMT) inducer (ILEI) facilitates EMT, invasion, and late aspects of metastasis
Kral M, Klimek C, Kutay B, Timelthaler G, Lendl T, Neuditschko B, Gerner C, Sibilia M, Csiszar A*.
FEBS J. 2017 Oct;284(20):3484-3505. doi: 10.1111/febs.14207. Epub 2017 Sep 14.
The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a non-interleukin-like fold and is active as a domain-swapped dimer
Jansson AM, Csiszar A, Maier J, Nyström AC, Axe E, Johansson P, Schiavone LH.
J Biol Chem. 2017 Sep 15;292(37):15501-15511. doi: 10.1074/jbc.M117.782904. Epub 2017 Jul 27.
Interleukin-like epithelial-to-mesenchymal transition inducer activity is controlled by proteolytic processing and plasminogen-urokinase plasminogen activator receptor system-regulated secretion during breast cancer progression
Csiszar A*, Kutay B, Wirth S, Schmidt U, Macho-Maschler S, Schreiber M, Alacakaptan M, Vogel GF, Aumayr K, Huber LA, Beug H.
Breast Cancer Res. 2014 Sep 9;16(5):433. doi: 10.1186/s13058-014-0433-7.
CDK8-mediated STAT1-S727 phosphorylation restrains NK cell cytotoxicity and tumor surveillance
Putz EM, Gotthardt D, Hörmann G, Csiszar A, Wirth S, Berger A, Straka E, Rigler D, Wallner B, Jamieson AM, Pickl WF, Zebedin-Brandl EM, Müller M, Decker T, Sexl V.
Cell Rep. 2013 Aug 15;4(3):437-44. doi: 10.1016/j.celrep.2013.07.012. Epub 2013 Aug 8.
- EU/Horizont 2020
- Fonds des Bürgermeisters der Bundeshauptstadt Wien (Agnes Csiszar)
- DOC-Stipendium der Österreichischen Akademie der Wissenschaften (Silvia Steinbauer)