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Omics · study · 2026

Dual Roles of SBSN in Renal Cell Carcinoma Progression and Tumor Thrombus Formation: Cell-Autonomous NF-κB-CD44 Activation and Paracrine Angiogenesis via IFI6

Listed in NCBI GEO

Renal cell carcinoma (RCC) is a highly vascularized malignancy with a propensity for venous invasion and tumor thrombus (TT) formation, yet the molecular mechanisms linking vascular aggression to tumor progression remain incompletely understood.

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In this study, we identify suprabasin (SBSN) as a key oncogenic mediator that is consistently upregulated in RCC tissues and further enriched in TT, correlating with poor patient prognosis.

Functional assays demonstrate that SBSN promotes RCC cell proliferation, migration, and invasion in vitro. Transcriptomic analysis reveals activation of the NF-κB signaling pathway in SBSN-overexpressing cells, with CD44 emerging as a critical downstream effector. We further delineate a novel SBSN-NF-κB-CD44 axis that drives malignant phenotypes in RCC cells.

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In vivo, SBSN knockdown attenuates tumor growth and induces a shift in epithelial-mesenchymal transition (EMT) markers. Clinically, SBSN expression in RCC tissue positively correlates with microvessel density (MVD). Mechanistically, tumor-secreted SBSN enhances angiogenesis through a paracrine pathway by upregulating the anti-apoptotic protein IFI6 in endothelial cells, thereby suppressing cleaved caspase-3 and Bax activation and promoting endothelial survival and tube formation.

Collectively, our findings uncover a dual role for SBSN in RCC progression: intrinsically via the NF-κB-CD44 axis to drive tumor cell aggressiveness, and extrinsically via the SBSN-IFI6 axis to promote angiogenesis and TT formation. This study positions SBSN as a potential prognostic biomarker and therapeutic target to disrupt both tumor growth and vascular support in advanced RCC.

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Life Sciences
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Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32786714 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title