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The article discusses the role of estrogen receptor-alpha (ERα) in hormone-dependent breast cancers and the challenge of overcoming mechanisms of endocrine resistance. The authors propose that changes in the transfer RNA (tRNA) pool and codon usage during cancer cell proliferation and differentiation may impact the functional properties of ERα. To test this hypothesis, they optimized the codon usage of an ERα synonymous coding sequence to frequencies observed in genes expressed in proliferating cells and found that this restored ERα activities to levels observed in differentiated cells, including enhanced transactivation function, increased interactions with nuclear receptor corepressors, and reduced interactions with certain kinases.
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