bioRxiv Science⌕ Search

Biology subjects

DIAZ, J.-J.

Publications and source records attributed to DIAZ, J.-J..

2 recordsLinked to original sources

Identification of ribosomal protein eL21 as a novel externalized protein and a potential target in triple negative breast cancer

Proteins normally localized in the intracellular compartments of healthy cells, have been observed at the surface of cancer cells, despite not having transmembrane domain or secretion signals. The unexpected localization of these externalized proteins is likely to reflect currently unknown functions. Their presence on the cell surface presents a unique opportunity for cancer therapy, enabling the development of antibody- or peptide-based strategies. In this study, we demonstrate the presence of an extracellular form of the ribosomal protein L21 (eL21) in triple negative breast cancer cells, using multiple complementary approaches and a broad set of antibodies. Importantly, we show that anti-eL21 antibodies induce a potent and immediate anti-proliferative effect characterized by cell cycle arrest and apoptosis. Our findings, uncover eL21 as novel ribosomal protein exhibiting extra-ribosomal functions. Finally, our study identifies eL21 as a promising therapeutic target in triple negative breast cancer.

cancer biology↗

Translational control of cell plasticity drives 5-FU tolerance

All routine clinical treatments for colorectal cancer include 5-fluorouracil (5-FU), which cannot counteract recurrence and metastases formation. As the pyrimidine analog 5-FU can impact multiple pathways including both DNA and RNA metabolism, studying its mode of actions could lead to improved therapies. Using a dedicated reporter system for lineage-tracing and deep translatome profiling we demonstrate that 5-FU causes some colorectal cancer cells to tolerate the drug, due to a durable translational reprogramming that sustains cell plasticity. This period of drug tolerance coincides with specific translational activation of genes coding for proteins with major pro-tumoral functions. We unravel a major unexpected translational overexpression of the pro-inflammatory and pro-tumoral IL-8 cytokine, alongside other anti-apoptotic, senescence-associated secretory phenotype and cancer-related senescence phenotype genes. Given the adverse prognostic implications of elevated IL-8 levels across various cancers, our findings suggest IL-8 targeting could counteract 5-FU resistance.

cancer biology↗