How ribosomes translate cancer

SO Sulima, IJF Hofman, K De Keersmaecker… - Cancer discovery, 2017 - AACR
Cancer discovery, 2017AACR
A wealth of novel findings, including congenital ribosomal mutations in ribosomopathies and
somatic ribosomal mutations in various cancers, have significantly increased our
understanding of the relevance of ribosomes in oncogenesis. Here, we explore the growing
list of mechanisms by which the ribosome is involved in carcinogenesis—from the hijacking
of ribosomes by oncogenic factors and dysregulated translational control, to the effects of
mutations in ribosomal components on cellular metabolism. Of clinical importance, the …
Abstract
A wealth of novel findings, including congenital ribosomal mutations in ribosomopathies and somatic ribosomal mutations in various cancers, have significantly increased our understanding of the relevance of ribosomes in oncogenesis. Here, we explore the growing list of mechanisms by which the ribosome is involved in carcinogenesis—from the hijacking of ribosomes by oncogenic factors and dysregulated translational control, to the effects of mutations in ribosomal components on cellular metabolism. Of clinical importance, the recent success of RNA polymerase inhibitors highlights the dependence on “onco-ribosomes” as an Achilles' heel of cancer cells and a promising target for further therapeutic intervention.
Significance: The recent discovery of somatic mutations in ribosomal proteins in several cancers has strengthened the link between ribosome defects and cancer progression, while also raising the question of which cellular mechanisms such defects exploit. Here, we discuss the emerging molecular mechanisms by which ribosomes support oncogenesis, and how this understanding is driving the design of novel therapeutic strategies. Cancer Discov; 7(10); 1069–87. ©2017 AACR.
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