Oncotarget

Research Papers:

PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation

Diana Barea Roldán, Matthias Grimmler, Christoph Hartmann, Stefanie Hubich-Rau, Tim Beißert, Claudia Paret, Giuseppe Cagna, Christoph Rohde, Stefan Wöll, Michael Koslowski, Özlem Türeci and Ugur Sahin _

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Oncotarget. 2020; 11:1862-1875. https://doi.org/10.18632/oncotarget.27582

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Abstract

Diana Barea Roldán1,*, Matthias Grimmler2,8,*, Christoph Hartmann2,9,*, Stefanie Hubich-Rau1,*, Tim Beißert1, Claudia Paret2,6, Giuseppe Cagna3,10, Christoph Rohde3,11, Stefan Wöll3,4, Michael Koslowski2,3,5,12, Özlem Türeci2,3,4,7 and Ugur Sahin1,4,6

1 TRON–Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

2 Formerly of TRON–Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

3 Formerly of Ganymed Pharmaceuticals AG, Mainz, Germany

4 Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany

5 Formerly of University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

6 University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

7 Ci3 Cluster for Individualized Immune Intervention, Mainz, Germany

8 Current address: DiaSys Diagnostic Systems GmbH, Holzheim, Germany

9 Current address: Merck KGaA, Darmstadt, Germany

10 Current address: Lonza Pharma & Biotech, Cologne, Germany

11 Current address: Merck KGaA, Darmstadt, Germany

12 Current address: GammaDelta Therapeutics, London, United Kingdom

* These authors contributed equally to this work

Correspondence to:

Ugur Sahin,email: Ugur.Sahin@uni-mainz.DE

Keywords: PLAC1; tumorigenesis; extracellular matrix; fibroblast growth factor; AKT

Received: November 14, 2019     Accepted: March 14, 2020     Published: May 19, 2020

ABSTRACT

PLAC1 (placenta enriched 1) is a mammalian trophoblast-specific protein. Aberrant expression of PLAC1 is observed in various human cancers, where it is involved in the motility, migration, and invasion of tumor cells, which are associated with the phosphoinositide 3-kinase (PI3K)/AKT pathway. We previously demonstrated that AKT activation mediates the downstream effects of PLAC1; however, the molecular mechanisms of PLAC1-induced AKT-mediated tumor-related processes are unclear. We studied human choriocarcinoma and breast cancer cell lines to explore the localization and receptor-ligand interactions, as well as the downstream effects of PLAC1. We show secretion and adherence of PLAC1 to the extracellular matrix, where it forms a trimeric complex with fibroblast growth factor 7 (FGF7) and its receptor, FGF receptor 2 IIIb (FGFR2IIIb). We further show that PLAC1 signaling via FGFR2IIIb activates AKT phosphorylation in cancer cell lines. As the FGF pathway is of major interest in anticancer therapeutic strategies, these data further promote PLAC1 as a promising anticancer drug target.


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