DDX3 modulates the tumor microenvironment via its role in endoplasmic reticulum-associated translation

Hung Hsi Chen, Hsin I. Yu, Rudy Rudy, Sim Lin Lim, Yi Fen Chen, Shu Hsing Wu, Shu Chun Lin, Muh Hwa Yang, Woan Yuh Tarn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Using antibody arrays, we found that the RNA helicase DDX3 modulates the expression of secreted signaling factors in oral squamous cell carcinoma (OSCC) cells. Ribo-seq analysis confirmed amphiregulin (AREG) as a translational target of DDX3. AREG exerts important biological functions in cancer, including promoting cell migration and paracrine effects of OSCC cells and reprogramming the tumor microenvironment (TME) of OSCC in mice. DDX3-mediated translational control of AREG involves its 3′-untranslated region. Proteomics identified the signal recognition particle (SRP) as an unprecedented interacting partner of DDX3. DDX3 and SRP54 were located near the endoplasmic reticulum, regulated the expression of a common set of secreted factors, and were essential for targeting AREG mRNA to membrane-bound polyribosomes. Finally, OSCC-associated mutant DDX3 increased the expression of AREG, emphasizing the role of DDX3 in tumor progression via SRP-dependent, endoplasmic reticulum-associated translation. Therefore, pharmacological targeting of DDX3 may inhibit the tumor-promoting functions of the TME.

Original languageEnglish
Article number103086
Issue number9
StatePublished - 24 Sep 2021


  • Cancer
  • Cell biology
  • Molecular biology


Dive into the research topics of 'DDX3 modulates the tumor microenvironment via its role in endoplasmic reticulum-associated translation'. Together they form a unique fingerprint.

Cite this