Ribosome biogenesis and new specialized ribosomes drives cancer cell plasticity

Currently there are no effective treatments that can cure metastatic breast cancer. One critical tumor cell plasticity program underlying metastatic spread is Epithelial-to-Mesenchymal Transition (EMT).

The overall goal of this proposal is to increase the understanding of how EMT is regulated, thereby contributing to the possibilities to expand the repertoire of novel therapies that target metastasis.Our previous work has demonstrated that EMT is accompanied by a dramatic reprogramming of RNA Polymerase I driven ribosome (rRNA) biogenesis.

We have also shown that continuous rRNA biogenesis is essential for the execution of the EMT program, hence representing a potential “Achilles’ heel” for metastatic spread.

In the proposed project we will determine how rRNA biogenesis and new and specialized metylated ribosomes are required for EMT and the pro-invasive mesenchymal gene expression program.

The studies will provide insights into the mechanisms by which post-EMT cells infiltrate and how the activation of ribosome biogenesis program controls the migratory program.

We will also investigate if targeting ribosome biogenesis can be used as a novel strategy to block tumor invasion and spread of metastatic breast cancers.

Using genome-wide transcriptomic and translatome methodologies, biochemical studies to probe physical ribosomes, sophisticated image analysis and pre-clinical breast cancer models, this proposal addresses a new area of EMT biology in a highly unique manner.