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

iScience

Hung-Hsi Chen¹  Woan-Yuh Tarn¹  Rudy Rudy¹  Hsin-I Yu¹  Muh-Hwa Yang²  Yi-Fen Chen³  Shu-Chun Lin³  Shu-Hsing Wu⁴  Sim-Lin Lim⁴ 

[1] Institute of Biomedical Sciences, Academia Sinica, 128 Academy Road Section 2, Nankang, Taipei 11529, Taiwan;Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan;Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan;Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan;

关键词: Molecular biology;    Cell biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown