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.