The Effects of Deregulated Ribosomal Biogenesis in Cancer

SIMPLE SUMMARY: Ribosomes are macromolecular complexes responsible for mRNA translation. When ribosome biogenesis is hyperactive or aberrant or ribosomal factors are mutated, ribosomopathies may occur, elevating cancer risks. This review aims to discuss recent research regarding the complex mechanism responsible for regulating ribosome biogenesis and delineate how the deregulation of this process is connected to cancer pathogenesis. Providing our perspective on how these observations provide opportunities for designing new targeted cancer treatments. In doing so, we hope to draw attention to persisting gaps in the literature and candidate targets involved in ribosomal biogenesis for cancer therapies to facilitate further research in this field. ABSTRACT: Ribosomes are macromolecular ribonucleoprotein complexes assembled from RNA and proteins. Functional ribosomes arise from the nucleolus, require ribosomal RNA processing and the coordinated assembly of ribosomal proteins (RPs), and are frequently hyperactivated to support the requirement for protein synthesis during the self-biosynthetic and metabolic activities of cancer cells. Studies have provided relevant information on targeted anticancer molecules involved in ribosome biogenesis (RiBi), as increased RiBi is characteristic of many types of cancer. The association between unlimited cell proliferation and alterations in specific steps of RiBi has been highlighted as a possible critical driver of tumorigenesis and metastasis. Thus, alterations in numerous regulators and actors involved in RiBi, particularly in cancer, significantly affect the rate and quality of protein synthesis and, ultimately, the transcriptome to generate the associated proteome. Alterations in RiBi in cancer cells activate nucleolar stress response-related pathways that play important roles in cancer-targeted interventions and immunotherapies. In this review, we focus on the association between alterations in RiBi and cancer. Emphasis is placed on RiBi deregulation and its secondary consequences, including changes in protein synthesis, loss of RPs, adaptive transcription and translation, nucleolar stress regulation, metabolic changes, and the impaired ribosome biogenesis checkpoint.