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Title: A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma
Author: Choi, Jee-Eun
Sebastián, Carlos
Ferrer, Christina M.
Lewis, Caroline A.
Sade Feldman, Moshe
LaSalle, Thomas
Gonye, Anna
Lopez, Begona G. C.
Abdelmoula, Walid M.
Regan, Michael S.
Cetinbas, Murat
Pascual, Gloria
Wojtkiewicz, Gregory R.
Silveira, Giorgia G.
Boon, Ruben
Ross, Kenneth N.
Tirosh, Itary
Saladi, Srinivas V.
Ellisen, Leif W.
Sadreyev, Ruslan I.
Aznar Benitah, Salvador
Agar, Nathalie Y. R.
Hacohen, Nir
Mostoslavsky, Raúl
Keywords: Càncer de coll
Càncer de cap
Proliferació cel·lular
Neck cancer
Head cancer
Cell proliferation
Issue Date: 22-Feb-2021
Publisher: Springer Nature
Abstract: Head and neck squamous cell carcinoma (SCC) remains among the most aggressive human cancers. Tumour progression and aggressiveness in SCC are largely driven by tumour-propagating cells (TPCs). Aerobic glycolysis, also known as the Warburg effect, is a characteristic of many cancers; however, whether this adaptation is functionally important in SCC, and at which stage, remains poorly understood. Here, we show that the NAD+-dependent histone deacetylase sirtuin 6 is a robust tumour suppressor in SCC, acting as a modulator of glycolysis in these tumours. Remarkably, rather than a late adaptation, we find enhanced glycolysis specifically in TPCs. More importantly, using single-cell RNA sequencing of TPCs, we identify a subset of TPCs with higher glycolysis and enhanced pentose phosphate pathway and glutathione metabolism, characteristics that are strongly associated with a better antioxidant response. Together, our studies uncover enhanced glycolysis as a main driver in SCC, and, more importantly, identify a subset of TPCs as the cell of origin for the Warburg effect, defining metabolism as a key feature of intra-tumour heterogeneity.
Note: Versió postprint del document publicat a:
It is part of: Nature Metabolism, 2021, Vol. 3, num. 2, p. 182-195
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ISSN: 2522-5812
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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