Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Laia Simó-Riudalbas (), Sandra Offner, Evarist Planet, Julien Duc, Laurence Abrami, Sagane Dind, Alexandre Coudray, Mairene Coto-Llerena, Caner Ercan, Salvatore Piscuoglio, Claus Lindbjerg Andersen, Jesper Bertram Bramsen and Didier Trono ()
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Laia Simó-Riudalbas: Ecole Polytechnique Fédérale de Lausanne
Sandra Offner: Ecole Polytechnique Fédérale de Lausanne
Evarist Planet: Ecole Polytechnique Fédérale de Lausanne
Julien Duc: Ecole Polytechnique Fédérale de Lausanne
Laurence Abrami: Ecole Polytechnique Fédérale de Lausanne
Sagane Dind: Ecole Polytechnique Fédérale de Lausanne
Alexandre Coudray: Ecole Polytechnique Fédérale de Lausanne
Mairene Coto-Llerena: University Hospital Basel
Caner Ercan: University Hospital Basel
Salvatore Piscuoglio: University Hospital Basel
Claus Lindbjerg Andersen: Aarhus University Hospital
Jesper Bertram Bramsen: Aarhus University Hospital
Didier Trono: Ecole Polytechnique Fédérale de Lausanne

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

Date: 2022
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DOI: 10.1038/s41467-022-32649-7

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