| First Author | Leineweber WD | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 9 | Pages | 110661 |
| PubMed ID | 39262774 | Mgi Jnum | J:354343 |
| Mgi Id | MGI:7732913 | Doi | 10.1016/j.isci.2024.110661 |
| Citation | Leineweber WD, et al. (2024) Divergent iron regulatory states contribute to heterogeneity in breast cancer aggressiveness. iScience 27(9):110661 |
| abstractText | Contact with dense collagen I (Col1) can induce collective invasion of triple negative breast cancer (TNBC) cells and transcriptional signatures linked to poor patient prognosis. However, this response is heterogeneous and not well understood. Using phenotype-guided sequencing analysis of invasive vs. noninvasive subpopulations, we show that these two phenotypes represent opposite sides of the iron response protein 1 (IRP1)-mediated response to cytoplasmic labile iron pool (cLIP) levels. Invasive cells upregulate iron uptake and utilization machinery characteristic of a low cLIP response, which includes contractility regulating genes that drive migration. Non-invasive cells upregulate iron sequestration machinery characteristic of a high cLIP response, which is accompanied by upregulation of actin sequestration genes. These divergent IRP1 responses result from Col1-induced transient expression of heme oxygenase I (HO-1), which cleaves heme and releases iron. These findings lend insight into the emerging theory that heme and iron fluxes regulate TNBC aggressiveness. |
