CELF1 is a central node in post-transcriptional regulatory programmes underlying EMT.

Area of Science:

• Molecular Biology
• Cancer Research
• Translational Regulation

Background:

• Translational regulation plays a critical role in tumor biology.
• Epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression and metastasis.

Purpose of the Study:

• To define translational regulatory programs driving EMT in breast epithelial cells.
• To identify key proteins and regulatory elements involved in EMT-driven tumor progression.

Main Methods:

• Utilized polyribosomal profiling to analyze translational activity.
• Identified cis-elements in mRNA 3'-untranslated regions (3'-UTRs).
• Investigated the role of the CELF1 protein in EMT and cancer progression.

Main Results:

• Discovered ten translationally regulated EMT drivers sharing a common GU-rich cis-element in their 3'-UTRs.
• Identified CELF1 protein as a direct binder of these cis-elements, regulating their translational activity.
• CELF1 protein is essential for mesenchymal transition and metastasis, and is overexpressed in human breast cancer tissues.

Conclusions:

• A novel 11-component genetic pathway, controlled by CELF1 at the translational level, drives EMT and tumor progression.
• This pathway is undetectable by traditional transcriptional profiling methods.
• CELF1 acts as a central node in controlling tumor metastasis and progression.