FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth.

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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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)

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:

Sabrina Cookman

Date Deposited:

11 May 2020 14:35

Last Modified:

11 May 2020 14:35

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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