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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Identification of ribosomal protein eL21 as a novel externalized protein and a target in triple-negative breast
Lucie Arnould1, Nina Radosevic-Robin2, Laura Duranton1
1Ribosome, Translation and Cancer team, DevWeCan Labex Laboratory, Institut Convergence PLAsCAN, Centre de recherche en cancérologie de Lyon, INSERM 1052, CNRS 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1, 69008, Lyon, France.
Abstract:
Proteins normally localized in the intracellular compartments of healthy cells have been observed at the surface of cancer cells, despite lacking a transmembrane domain or secretion signals. This unexpected localization likely reflects yet-unknown functions and presents a unique opportunity to develop cancer cell-specific antibody- or peptide-based therapeutic strategies. While ribosomal proteins (RPs) are primarily involved in translation, several display moonlighting functions in the cytoplasm and nucleus. In this study, we uncover an extracellular form of the ribosomal protein L21 (eL21) in triple-negative breast cancer (TNBC) cells. Using complementary approaches and a broad set of antibodies, we demonstrate that eL21 localizes to the surface of cancer cells. Remarkably, we show that anti-eL21 antibodies trigger a potent, rapid and dose-dependent anti-proliferative effect, including TNBC cell cycle arrest and apoptosis. These findings identify eL21 as a novel ribosomal protein with extra-ribosomal functions at the cancer cell surface and highlight its potential as a therapeutic target in TNBC.
Insights
Extracellular ribosomal protein L21 (eL21) was found on triple-negative breast cancer (TNBC) cells. Antibodies targeting eL21 demonstrated significant anti-cancer effects, suggesting eL21 as a potential therapeutic target for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Intracellular proteins are found on cancer cell surfaces without typical export signals.
- Ribosomal proteins (RPs) have known cytoplasmic/nuclear roles, but extracellular functions are emerging.
- Triple-negative breast cancer (TNBC) presents a challenge for targeted therapies.
Purpose of the Study:
- To investigate the presence and function of extracellular ribosomal protein L21 (eL21) in TNBC.
- To explore eL21 as a potential therapeutic target for TNBC.
Main Methods:
- Utilized complementary biochemical and immunological approaches.
- Employed a diverse panel of antibodies for detection and functional assays.
- Investigated eL21 localization on TNBC cell surfaces.
Main Results:
- Identified and confirmed extracellular eL21 on the surface of TNBC cells.
- Demonstrated that anti-eL21 antibodies induce rapid, dose-dependent anti-proliferative effects.
- Observed TNBC cell cycle arrest and apoptosis mediated by anti-eL21 antibodies.
Conclusions:
- Ribosomal protein L21 exhibits novel extra-ribosomal functions at the cancer cell surface.
- eL21 is a potential cell surface biomarker and therapeutic target for TNBC.
- Targeting eL21 with antibodies shows promise for TNBC treatment strategies.
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