Antibiotic-disrupted ribosome biogenesis facilitates tumor chemokine superinduction

Area of Science:

• Molecular Biology
• Cancer Biology
• Cellular Stress Response

Background:

• Ribosomes play a critical role in cellular stress responses, influencing inflammation and tumorigenesis.
• Dysfunctional ribosome activity is linked to pathological processes in cancer.

Purpose of the Study:

• To investigate the impact of ribosome biogenesis on tumor chemokines in intestinal cancer.
• To elucidate the molecular mechanisms by which ribosome stress influences chemokine expression and cancer malignancy.

Main Methods:

• Inhibition of ribosome biogenesis using actinomycin D (ActD) in intestinal cancer cells under endoplasmic reticulum stress.
• Analysis of chemokine expression at transcriptional and post-transcriptional levels.
• Investigation of the roles of p53, macrophage inhibitory cytokine 1 (MIC-1), TGF-β-activated kinase 1 (TAK-1), and nuclear factor-kappa B (NF-κB) signaling pathways.
• Validation using clinical transcriptome datasets and analysis of patient prognoses.

Main Results:

• Ribosome biogenesis inhibition significantly enhanced chemokine expression in intestinal cancer cells experiencing endoplasmic reticulum stress.
• This enhancement was mediated by p53 and MIC-1, which activated TAK-1 and NF-κB signaling.
• Clinical data confirmed MIC-1 as a positive regulator of chemokines and ribosome biogenesis genes in tumor tissues.
• MIC-1-associated chemokine expression correlated with poor prognoses in colorectal cancer patients.

Conclusions:

• Ribosome biogenesis inhibition drives pro-tumoral chemokine expression through MIC-1 signaling in intestinal cancer.
• The p53-MIC-1-TAK-1-NF-κB axis is a key mechanism regulating chemokine induction under ribosomal stress.
• This pathway represents a novel target for developing therapeutic strategies against malignant inflammation in cancer.