Biology subjects

CATEZ, F.

Publications and source records attributed to CATEZ, F..

4 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2025

Ribosome biogenesis is a therapeutic vulnerability in paediatric neuroblastoma

BackgroundNeuroblastoma is a heterogeneous malignant paediatric tumor with prognosis depending on patient age and disease stage. Current treatment strategies rely on four key diagnostic criteria: age, histological stage, MYCN gene status, and genomic profile. It has been reported that MYC oncogenic activity depends on ribosome biogenesis, whose hyperactivation in cancer cells supports their high proliferative capacity, and thus represent a potential therapeutic target. Methodswe utilized the well-established IMR-32 cell line along with a panel of patient-derived neuroblastoma cell lines with varying MYCN status, which we previously established. Additionally, we generated an IMR-32 cell line expressing an shRNA targeting the ribosome biogenesis factor fibrillarin (FBL). Cell growth, apoptosis markers, and cell cycle regulators were analyzed. Expression of ribosome biogenesis factors was assessed using publicly available datasets and RT-qPCR data from an in-house neuroblastoma cohort. ResultsWe explored whether ribosome biogenesis represents a vulnerability in neuroblastoma. Our findings demonstrate that inhibition of RNA polymerase I using CX-5461 and BMH-21 suppressed cell proliferation at nanomolar concentrations and induced ribosomal stress, leading to activation of apoptosis and the p21 pathway. Furthermore, we identified FBL as a marker of poor prognosis in neuroblastoma. Consistently, FBL knockdown reduced neuroblastoma cell proliferation, supporting its potential as a therapeutic target. ConclusionOur study reinforces the therapeutic potential of ribosome biogenesis inhibition in neuroblastoma and expands the list of potential targets to include rRNA maturation factors. These findings highlight the promise of targeting ribosome biogenesis as a novel approach for neuroblastoma treatment.

cancer biology↗

bioRxiv2024

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↗

bioRxiv2021

RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells.

Embryonic stem cell (ESC) fate decisions are regulated by a complex molecular circuitry that requires tight and coordinated gene expression regulations at multiple levels from chromatin organization to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key regulatory pathways that efficiently control stem cell homeostasis. However, the molecular mechanisms underlying the regulation of these pathways remain largely unknown to date. Here, we analyzed the expression, in mouse ESCs, of over 300 genes involved in ribosome biogenesis and we identified RSL24D1 as the most differentially expressed between self-renewing and differentiated ESCs. RSL24D1 is highly expressed in multiple mouse pluripotent stem cell models and its expression profile is conserved in human ESCs. RSL24D1 is associated with nuclear pre-ribosomes and is required for the maturation and the synthesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors, including POU5F1 and NANOG, as well as components of the polycomb repressive complex 2 (PRC2). Consistently, RSL24D1 is required for mouse ESC self-renewal and proliferation. Taken together, we show that RSL24D1-dependant ribosome biogenesis is required to both sustain the expression of pluripotent transcriptional programs and silence developmental programs, which concertedly dictate ESC homeostasis.

developmental biology↗