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ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

ABSTRACT: ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

PROVIDER: PRJEB50323 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR8057621.fastq.gz	Fastqsanger.gz
	ERR8057622.fastq.gz	Fastqsanger.gz
	ERR8057623.fastq.gz	Fastqsanger.gz
	ERR8057624.fastq.gz	Fastqsanger.gz
	ERR8057625.fastq.gz	Fastqsanger.gz

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ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

Project description:ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

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ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

Project description:We identified a novel uncharacterized short isoform of the Roundabout Guidance Receptor 3 (ROBO3) encoding for the C-terminal domain of the protein and lacking transmembrane region. We established an important role for the so-called ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving the resistance of Basal-like breast cancer cells to cytotoxic drugs.

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ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

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Project description:ROBO3s: a novel ROBO3 shot isoform promoting breast cancer aggressiveness

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

Project description: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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