Polyol pathway links glucose metabolism to the aggressiveness of cancer cells

Journal article


Publication Details

Author(s): Schwab A, Siddiqui A, Vazakidou ME, Napoli F, Böttcher M, Menchicchi B, Raza U, Saatci O, Krebs A, Ferrazzi F, Rapa I, Dettmer-Wilde K, Waldner M, Ekici AB, Rasheed SAK, Mougiakakos D, Oefner PJ, Sahin O, Volante M, Greten FR, Brabletz T, Ceppi P
Journal: Cancer Research
Publication year: 2018
ISSN: 0008-5472


Abstract

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 TGF-? signature genes. Excess glucose was found to promote EMT through autocrine TGF-? 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.


FAU Authors / FAU Editors

Böttcher, Martin Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Brabletz, Thomas Prof. Dr. med.
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Ceppi, Paolo Dr.
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe I Dr.Körner
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Ferrazzi, Fulvia Dr.
Humangenetisches Institut
Krebs, Angela
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Menchicchi, Bianca Dr.
Erlangen Graduate School in Advanced Optical Technologies
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie
Schwab, Annemarie
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe I Dr.Körner
Siddiqui, Aarif
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe I Dr.Körner
Vazakidou, Maria Eleni
Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe I Dr.Körner
Waldner, Maximilian Prof. Dr.
Professur für Funktionelle Bildgebung in der Medizin


External institutions with authors

Bilkent University / Bilkent Üniversitesi
Institut für Tumorbiologie und experimentelle Therapie / Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus
National University of Singapore (NUS)
Universität Regensburg
University of Turin / Università degli Studi di Torino (UNITO)


How to cite

APA:
Schwab, A., Siddiqui, A., Vazakidou, M.E., Napoli, F., Böttcher, M., Menchicchi, B.,... Ceppi, P. (2018). Polyol pathway links glucose metabolism to the aggressiveness of cancer cells. Cancer Research. https://dx.doi.org/10.1158/0008-5472.CAN-17-2834

MLA:
Schwab, Annemarie, et al. "Polyol pathway links glucose metabolism to the aggressiveness of cancer cells." Cancer Research (2018).

BibTeX: 

Last updated on 2018-21-11 at 10:23