The impact of ribosome biogenesis in cancer: from proliferation to metastasis

Abstract

The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome biogenesis, notably through RNA Pol I inhibition, elicits a stress response marked by nucleolar integrity loss, and subsequent G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, rendering ribosomal RNA synthesis a potential therapeutic vulnerability. The review further explores targeting ribosome biogenesis vulnerabilities as a promising strategy to disrupt global ribosome production, presenting therapeutic opportunities for cancer treatment.

SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma

“…Elevated ribosome biogenesis and translation output are hallmarks of cancer 27 , and overexpression of ribosome proteins has been linked to enhanced cancer proliferation and metastasis 32,33 . Recent studies have expanded the scope to include rRNA modifications in cancer 34,35 , and some modifications exhibit variable levels between cancer and normal tissues, suggesting a mechanism for ribosome heterogeneity 36 .…”

Editorial: Translational control in cancer

“…Translational reprogramming is also made possible for cancer cells by hijacking ribosome biogenesis. Hwang and Denicourt introduce us to how this process is indeed tightly intertwined with cancer hallmarks ( 4 ). They highlight that, from stemness maintenance and the epithelial-mesenchymal transition to stress response, oncogenic signaling pathways are heavily affected by the alteration in this critical cellular process, also presenting relevant therapeutic opportunities.…”