ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness
| Autor: | Marcel Werner, Anna Dyas, Iwan Parfentev, Geske E. Schmidt, Iga K. Mieczkowska, Lukas C. Müller-Kirschbaum, Claudia Müller, Stefan Kalkhof, Oliver Reinhardt, Henning Urlaub, Frauke Alves, Julia Gallwas, Evangelos Prokakis, Florian Wegwitz |
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| Přispěvatelé: | Publica, Werner, Marcel [0000-0002-6328-048X], Mieczkowska, Iga K [0000-0002-3684-3945], Müller-Kirschbaum, Lukas C [0000-0003-1885-6694], Prokakis, Evangelos [0000-0001-9297-1821], Wegwitz, Florian [0000-0003-0750-6998], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: |
Proteomics
96/106 Cancer Research 82/58 Immunology article Antineoplastic Agents Breast Neoplasms Mammary Neoplasms Animal Receptors Cell Surface 631/67/1347 Cell Biology 631/67/1857 38/91 Mice Cellular and Molecular Neuroscience 13/100 42/89 631/67/395 Animals Humans Protein Isoforms 64/60 Female 631/67/71 |
| Zdroj: | Cell Death and Disease Cell Death Dis. 13:762 (2022) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-022-05197-7 |
| Popis: | Basal-like breast cancer (BLBC) is a highly aggressive breast cancer subtype frequently associated with poor prognosis. Due to the scarcity of targeted treatment options, conventional cytotoxic chemotherapies frequently remain the standard of care. Unfortunately, their efficacy is limited as BLBC malignancies rapidly develop resistant phenotypes. Using transcriptomic and proteomic approaches in human and murine BLBC cells, we aimed to elucidate the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in these mammary tumors. Specifically, we identified and characterized a novel short isoform of Roundabout Guidance Receptor 3 (ROBO3s), upregulated in BLBC in response to chemotherapy and encoding for a protein variant lacking the transmembrane domain. We established an important role for the ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving resistance of BLBC cells to cytotoxic drugs. By uncovering the conservation of ROBO3s expression across multiple cancer types, as well as its association with reduced BLBC-patient survival, we emphasize its potential as a prognostic marker and identify a novel attractive target for anti-cancer drug development. |
| Databáze: | OpenAIRE |
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