The Secret Life of Translation Initiation in Prostate Cancer

Abstract

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. Despite the advances understanding the molecular processes driving the onset and progression of this disease, as well as the continued implementation of screening programs, PCa still remains a significant cause of morbidity and mortality, in particular in low-income countries. It is only recently that defects of the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template, have begun to gain attention as an important cause of cancer development in different human tissues, including prostate. In particular, the initiation step of translation has been established to play a key role in tumorigenesis. In this review, we discuss the state-of-the-art of three key aspects of protein synthesis in PCa, namely, misexpression of translation initiation factors, dysregulation of the major signaling cascades regulating translation, and the therapeutic strategies based on pharmacological compounds targeting translation as a novel alternative to those based on hormones controlling the androgen receptor pathway.

SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy

“…Cancer cell survival depends on the coordinated activation of translation initiation factors and major signaling cascades regulating translation that are implicated in a broad range of cellular processes [ 25 , 26 ]. Our analysis highlighted the overrepresentation of molecular networks associated with transcriptional and translational regulation, which might allow them to adapt to anti-androgen induced cellular stress.…”

Eukaryotic translation initiation factors as promising targets in cancer therapy

“…The 4E-BPs compete with eIF4G for its binding site on eIF4E, the binding of 4E-BPs to eIF4E is reversible and regulated by mTORC1-dependent phosphorylation of 4E-BPs, thus when phosphorylated by mTORC1, hyperphosphorylated 4E-BPs are incapable of binding eIF4E, enabling the association of eIF4E with eIF4G and the formation of eIF4F complex [ 30 ]. Elevated levels of phosphorylated 4E-BP1, which are suggestive of higher levels of eIF4F complex, were detected in advanced prostate cancer [ 146 , 147 ]. Similarly, reduced 4E-BP1 expression and elevated levels of 4E-BP1 phosphorylation in some cancers were positively correlated with higher grade tumors and reduced survival [ 148 , 149 ].…”

Identification of core genes associated with prostate cancer progression and outcome via bioinformatics analysis in multiple databases

“…(M-R) The ROC curve and AUC of the six core genes were showed. Full-size  DOI: 10.7717/peerj.8786/ fig-4 mortality, particularly in low-income countries (Hernández et al, 2019). However, the formation mechanisms of PCa are incomprehensive.…”