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Werner, M. ; Dyas, A.* ; Parfentev, I.* ; Schmidt, G.E.* ; Mieczkowska, I.K.* ; Mueller-Kirschbaum, L.C.* ; Müller, C.* ; Kalkhof, S.* ; Reinhardt, O.* ; Urlaub, H.* ; Alves, F.* ; Gallwas, J.* ; Prokakis, E.* ; Wegwitz, F.*

ROBO3s: A novel ROBO3 short isoform promoting breast cancer aggressiveness.

Cell Death Dis. 13:762 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Journal Cell Death & Disease
Quellenangaben Volume: 13, Issue: 9, Pages: , Article Number: 762 Supplement: ,
Publisher Nature Publishing Group
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Grants Erich und Gertrud Roggenbuck-Stiftung (Erich and Gertrud Roggenbuck Foundation)