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Cancers 2014, 6(3), 1579-1596; doi:10.3390/cancers6031579
Article

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

1,†,* , 2,†
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, 3
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 and 1,*
Received: 13 May 2014; in revised form: 3 July 2014 / Accepted: 16 July 2014 / Published: 31 July 2014
(This article belongs to the Special Issue STAT3 Signalling in Cancer: Friend or Foe)
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Abstract: STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3C/C) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.
Keywords: STAT3; metabolism; Warburg effect; aerobic glycolysis; cellular transformation; mitochondrial activity STAT3; metabolism; Warburg effect; aerobic glycolysis; cellular transformation; mitochondrial activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Camporeale, A.; Demaria, M.; Monteleone, E.; Giorgi, C.; Wieckowski, M.R.; Pinton, P.; Poli, V. STAT3 Activities and Energy Metabolism: Dangerous Liaisons. Cancers 2014, 6, 1579-1596.

AMA Style

Camporeale A, Demaria M, Monteleone E, Giorgi C, Wieckowski MR, Pinton P, Poli V. STAT3 Activities and Energy Metabolism: Dangerous Liaisons. Cancers. 2014; 6(3):1579-1596.

Chicago/Turabian Style

Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria. 2014. "STAT3 Activities and Energy Metabolism: Dangerous Liaisons." Cancers 6, no. 3: 1579-1596.



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