> Detailanzeige

Schwab, Annemarie; Siddiqui, Aarif; Vazakidou, Maria Eleni; Napoli, Francesca; Böttcher, Martin; Menchicchi, Bianca; Raza, Umar; Saatci, Özge; Krebs, Angela M.; Ferrazzi, Fulvia; Rapa, Ida; Dettmer-Wilde, Katja; Waldner, Maximilian J.; Ekici, Arif B.; Rasheed, Suhail Ahmed Kabeer; Mougiakakos, Dimitrios; Oefner, Peter J.; Sahin, Ozgur; Volante, Marco; Greten, Florian R.; Brabletz, Thomas; Ceppi, Paolo

Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells
  • Beteiligte: Schwab, Annemarie; Siddiqui, Aarif; Vazakidou, Maria Eleni; Napoli, Francesca; Böttcher, Martin; Menchicchi, Bianca; Raza, Umar; Saatci, Özge; Krebs, Angela M.; Ferrazzi, Fulvia; Rapa, Ida; Dettmer-Wilde, Katja; Waldner, Maximilian J.; Ekici, Arif B.; Rasheed, Suhail Ahmed Kabeer; Mougiakakos, Dimitrios; Oefner, Peter J.; Sahin, Ozgur; Volante, Marco; Greten, Florian R.; Brabletz, Thomas; Ceppi, Paolo
  • Erschienen: American Association for Cancer Research (AACR), 2018
  • Erschienen in: Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/0008-5472.can-17-2834
  • ISSN: 0008-5472; 1538-7445
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Cancer cells alter their metabolism to support their malignant properties. In this study, we report that the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) strongly correlates with epithelial-to-mesenchymal transition (EMT). This association was confirmed in samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels, and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGFβ signature genes. Excess glucose was found to promote EMT through autocrine TGFβ stimulation, while PP-deficient cells were refractory to glucose-induced EMT. These data show that PP represents a molecular link between glucose metabolism, cancer differentiation, and aggressiveness, and may serve as a novel therapeutic target.</jats:p><jats:p>Significance: A glucose-transforming pathway in TGFβ-driven epithelial-to-mesenchymal transition provides novel mechanistic insights into the metabolic control of cancer differentiation. Cancer Res; 78(7); 1604–18. ©2018 AACR.</jats:p>
  • Zugangsstatus: Freier Zugang