Ribosome biogenesis, the multi-step process of synthesis, modification, and assembly of ribosomal RNA and proteins into mature ribosomes, is universally upregulated in cancers. Due to their increased anabolic demands, cancer cells are often highly sensitive to inhibition of ribosome biogenesis, and several current anti-cancer therapies function by targeting ribosome biogenesis, making it an exciting candidate for further therapeutic exploration. Our research has revealed two novel mechanisms through which tumour cells enhance their ribosome biogenesis. One mechanism acts at the level of ribosomal protein synthesis, by coupling cell migration with increased synthesis of ribosomal proteins, leading to enhanced ribosome biogenesis in aggressive cancer cells that invade into their surroundings. The second mechanism enhances ribosomal RNA synthesis via a phospho-dependent RNA binding switch downstream of oncogenic MAPK signalling, leading to upregulation of ribosome biogenesis upon RAS transformation. We demonstrate that targeting each of these pathways inhibits tumour growth in vivo, highlighting their potential as novel therapeutic targets.
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Dr Faraz Mardakheh, BSc, PhD.
I received my undergraduate degree in 2006 from University of Birmingham, before joining the laboratory of Professor John Heath to study feedback regulation of Receptor Tyrosine Kinase signalling. After completing my PhD, I moved to London in 2010 to study cancer cell migration and invasion as a postdoc in the laboratory of the late Professor Chris Marshall. Thanks to an unexpected discovery during my post-doc, I started working on RNA Binding Proteins (RBPs). Then in 2017, I received an MRC Career Development Award fellowship to start my own research group at the Barts Cancer Institute, Queen Mary University of London, and study RBPs in the context of cancer. By using various omics approaches, my research aim is to identify and characterise RBPs whose activities are altered in cancer, leading to disease development and progression.
For further information visit Mardakheh Lab
