ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
03 09 2022
03 09 2022
Historique:
received:
11
03
2022
accepted:
17
08
2022
revised:
12
08
2022
entrez:
3
9
2022
pubmed:
4
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36057630
doi: 10.1038/s41419-022-05197-7
pii: 10.1038/s41419-022-05197-7
pmc: PMC9440919
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Isoforms
0
ROBO3 protein, human
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
762Informations de copyright
© 2022. The Author(s).
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