FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth
Giorgio Ramadori,
Rafael M. Ioris,
Zoltan Villanyi,
Raquel Firnkes,
Olesya O. Panasenko,
George Allen,
Georgia Konstantinidou,
Ebru Aras,
Xavier Brenachot,
Tommasina Biscotti,
Anne Charollais,
Michele Luchetti,
Fedor Bezrukov,
Alfredo Santinelli,
Muntaha Samad,
Pierre Baldi,
Martine A. Collart,
Roberto Coppari
Affiliations
Giorgio Ramadori
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Corresponding author
Rafael M. Ioris
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Zoltan Villanyi
Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics, Facutly of Medicine, University of Geneva, 1211 Geneva, Switzerland
Raquel Firnkes
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Olesya O. Panasenko
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Department of Infectious Diseases, Hôpitaux Universitaires de Genève, Genève, Switzerland
George Allen
Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics, Facutly of Medicine, University of Geneva, 1211 Geneva, Switzerland
Georgia Konstantinidou
Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
Ebru Aras
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Xavier Brenachot
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Tommasina Biscotti
Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60020 Ancona, Italy
Anne Charollais
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Michele Luchetti
Clinica Medica, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, 60020 Ancona, Italy
Fedor Bezrukov
School of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Alfredo Santinelli
Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60020 Ancona, Italy
Muntaha Samad
Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA
Pierre Baldi
Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA
Martine A. Collart
Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics, Facutly of Medicine, University of Geneva, 1211 Geneva, Switzerland; Corresponding author
Roberto Coppari
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Corresponding author
Summary: Cancer therapy is limited, in part, by lack of specificity. Thus, identifying molecules that are selectively expressed by, and relevant for, cancer cells is of paramount medical importance. Here, we show that peptidyl-prolyl-cis-trans-isomerase (PPIase) FK506-binding protein 10 (FKBP10)-positive cells are present in cancer lesions but absent in the healthy parenchyma of human lung. FKBP10 expression negatively correlates with survival of lung cancer patients, and its downregulation causes a dramatic diminution of lung tumor burden in mice. Mechanistically, our results from gain- and loss-of-function assays show that FKBP10 boosts cancer growth and stemness via its PPIase activity. Also, FKBP10 interacts with ribosomes, and its downregulation leads to reduction of translation elongation at the beginning of open reading frames (ORFs), particularly upon insertion of proline residues. Thus, our data unveil FKBP10 as a cancer-selective molecule with a key role in translational reprogramming, stem-like traits, and growth of lung cancer. : Ramadori et al. show that the peptidyl-prolyl-cis-trans-isomerase FKBP10 is selectively expressed in lung cancer cells, and its expression negatively correlates with patient survival. FKBP10 is associated with ribosomes and regulates translation elongation, in particular upon insertion of proline, hence supporting lung cancer growth and stem-like traits.
