Ribosome Biogenesis and Cancer Development

Introduction

Ribosome biogenesis is a multi-step process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoints and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyper-activation of ribosome biogenesis. Emerging evidence reveals that cancer cells harbor a specialized class of ribosomes which facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring.

Fig. 1 Identified inhibitors target different stages of rRNA processing.¹

Ribosome Biogenesis and Cancer Development

The alterations of nucleolar morphology observed in cancer cells directly reflect the hyper activation of ribosome production. Generally, tumor cells are addicted to increased ribosome production and translational activity. It is largely assumed that cancer cells become addicted to ribosomes owing to their enhanced need for protein production to sustain their unrestricted growth. The abnormal oncogenic signaling of cancer cells prevents the efficient feedback control that coordinates the synthesis of rRNAs and ribosomal proteins (RPs), and eventually leads to nucleolar stress and apoptosis. Increased ribosome biogenesis is a general trend in cancer cells which is important for cell transformation and tumorigenesis. Theoretically, increased ribosome production in cancer cells is caused by the dysregulation of the three RNA polymerases by molecular mechanisms involving cancer-promoting proteins, including major oncogenic and tumor suppressive pathways, like mTOR, c-Myc, p53, PTEN, and pRb.

Present research has stimulated the development of new drugs designed to induce a selective inhibition of ribosomal biogenesis without the genotoxic effects typical of most currently used anticancer drugs. Considering the connection established between ribosome biogenesis and cancer, it will be worthy to define the role of ribosome biogenesis in cancer from the following aspects.

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Reference

1. Awad, Dominik, et al. "Inhibiting eukaryotic ribosome biogenesis." BMC biology 17.1 (2019): 1-16.