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Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism

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Cacace, Andrea [UCL] Sboarina, Martina [UCL] Vazeille, Thibaut [UCL] Sonveaux, Pierre [UCL]

Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. While both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione. Extracellular glutamine activates transcription factor STAT3, which is necessary and sufficient to mediate the proliferative effects of glutamine on glycolytic and in oxidative cancer cells. Glutamine also activates transcription factors HIF-1, mTOR and c-Myc, but these factors do not mediate the effects of glutamine on cancer cell proliferation. Our findings shed a new light on the anticancer effects of L-asparaginase that possesses glutaminase activity and converts glutamine into glutamate extracellularly. Conversely, cancer resistance to treatments that block glutamine metabolism could arise from glutamine-independent STAT3 re-activation.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès interdit
Publication date 2017
Language Anglais
Journal information "Oncogene : including Oncogene Reviews" - Vol. 36, no. 15, p. 2074-2084 (2017)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 0950-9232
e-issn 1476-5594
Publication status Publié
Affiliation UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
Links
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Bibliographic reference Cacace, Andrea ; Sboarina, Martina ; Vazeille, Thibaut ; Sonveaux, Pierre. Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism. In: Oncogene : including Oncogene Reviews, Vol. 36, no. 15, p. 2074-2084 (2017)
Permanent URL http://hdl.handle.net/2078.1/176818