Cell Reports
Volume 30, Issue 11, 17 March 2020, Pages 3851-3863.e6
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Article
FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth

https://doi.org/10.1016/j.celrep.2020.02.082Get rights and content
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Highlights

  • FKBP10 is selectively expressed in lung cancer cells

  • Expression of FKBP10 negatively correlates with survival of lung cancer patients

  • FKBP10 downregulation suppresses cancer growth and cancer stem-like features

  • FKBP10 regulates translation elongation in particular upon insertion of proline

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.

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