Transposon-activated POU5F1B Promotes Colorectal Cancer Growth and Metastasis

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 20

PMID 35987910

Authors

Laia Simo-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

Didier Trono

Affiliations

Soon will be listed here.

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.

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