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Divergent iron regulatory states contribute to heterogeneity in breast cancer aggressiveness.
Leineweber, William D; Rowell, Maya Z; Ranamukhaarachchi, Sural K; Walker, Alyssa; Li, Yajuan; Villazon, Jorge; Mestre-Farrera, Aida; Hu, Zhimin; Yang, Jing; Shi, Lingyan; Fraley, Stephanie I.
Afiliación
  • Leineweber WD; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Rowell MZ; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ranamukhaarachchi SK; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Walker A; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Li Y; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Villazon J; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Mestre-Farrera A; Department of Pharmacology, Moores Cancer Center, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Hu Z; Department of Pharmacology, Moores Cancer Center, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Yang J; Department of Pharmacology, Moores Cancer Center, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Shi L; Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Fraley SI; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
iScience ; 27(9): 110661, 2024 Sep 20.
Article en En | MEDLINE | ID: mdl-39262774
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos