The plasticity of mRNA translation during cancer progression and therapy resistance

Area of Science:

• Molecular Biology
• Cancer Biology
• Gene Expression Regulation

Background:

• Aberrant oncogenic signaling (e.g., PI3K-AKT-mTOR, RAS-MAPK, MYC) and microenvironmental stress (hypoxia, nutrient deprivation) profoundly impact cancer cells.
• Cells dynamically adapt to these stimuli through rapid, specific changes in protein synthesis, known as translational rewiring.
• This rewiring is crucial for shaping cancer phenotypes, driving tumor initiation, progression, and therapeutic resistance.

Purpose of the Study:

• To review the plasticity of mRNA translation in cancer.
• To elucidate the diverse regulatory mechanisms of mRNA translation in response to oncogenic and microenvironmental cues.
• To describe the influence of translational control on cancer cell plasticity, the tumor microenvironment, and response to anticancer therapies.

Main Methods:

• Review of existing literature on mRNA translation regulation in cancer.
• Analysis of mechanisms involving translation factors (e.g., eukaryotic initiation factor 4F (eIF4F), eIF2), RNA-binding proteins, tRNAs, and ribosomal RNAs.
• Examination of the impact of translational control on cancer phenotypes and the tumor microenvironment.

Main Results:

• mRNA translation exhibits significant plasticity, enabling cancer cells to adapt to diverse internal and external pressures.
• Specific translational control mechanisms are modulated by oncogenic pathways and microenvironmental stress.
• Altered mRNA translation influences cancer cell phenotypic plasticity and the tumor microenvironment, impacting disease progression.

Conclusions:

• Translational control is a critical determinant of cancer cell behavior and therapeutic response.
• The intricate regulation of mRNA translation presents a promising target for novel anticancer strategies.
• Understanding translational plasticity is key to developing more effective cancer treatments.