Omics · study · 2026
Non-canonical function of transferrin receptor-1 promotes breast cancer metastasis by activating HCK-STAT3-MMP9 signaling
Listed in NCBI GEO
Transferrin receptor 1 (TfR-1), a key mediator of cellular iron uptake, is significantly upregulated across a broad spectrum of malignancies, and its overexpression highly correlated with poor clinical outcomes, such as in breast cancer.
Description
However, its precise role in breast cancer progression remains unclear. In this study, analysis of clinical samples from breast cancer patients and public databases demonstrated that high level of TfR-1 in breast cancer samples is strongly associated with metastasis.
We further verified that elevated TfR-1 enhances the proliferative and metastatic potential of breast cancer cells both in vitro and in vivo. Mechanistically, we uncovered an unexpected protein kinase activity of TfR-1, which directly phosphorylates hematopoietic cell kinase (HCK). Concurrently, TfR-1 activates ubiquitin-specific protease 32 (USP32), thereby stabilizing HCK protein.
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Subsequently, phosphorylated HCK facilitates the activation of the transcription factor STAT3, resulting in increased expression and secretion of matrix metalloproteinase 9 (MMP9). Moreover, HCK exerts reciprocal phosphorylation on TfR-1, forming a positive feedback loop. Collectively, our findings unravel a novel molecular mechanism underlying TfR-1-mediated metastasis in breast cancer, highlighting the importance of TfR-1’s non-canonical phosphorylation activity beyond its established role in iron transport, and identifying potential therapeutic targets for cancer intervention.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318333 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318333 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1418596 ncbi.nlm.nih.gov/bioproject/PRJNA1418596 ↗
project · from NCBI GEO
- PubMed 42437977 pubmed.ncbi.nlm.nih.gov/42437977 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE318333 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |