Ramadori, Giorgio; Ioris, Rafael M; Villanyi, Zoltan; Firnkes, Raquel; Panasenko, Olesya O; Allen, George; Konstantinidou, Georgia; Aras, Ebru; Brenachot, Xavier; Biscotti, Tommasina; Charollais, Anne; Luchetti, Michele; Bezrukov, Fedor; Santinelli, Alfredo; Samad, Muntaha; Baldi, Pierre; Collart, Martine A; Coppari, Roberto (2020). FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth. Cell reports, 30(11), pp. 3851-863. Cell Press 10.1016/j.celrep.2020.02.082
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Konstantindidou_FKBP10 regulates protein translation to sustain lung cancer growth.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (4MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Konstantinidou, Georgia |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2211-1247 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Celine Joray |
Date Deposited: |
11 May 2020 14:35 |
Last Modified: |
05 Dec 2022 15:38 |
Publisher DOI: |
10.1016/j.celrep.2020.02.082 |
PubMed ID: |
32187554 |
BORIS DOI: |
10.7892/boris.143749 |
URI: |
https://boris.unibe.ch/id/eprint/143749 |
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