AUTHOR=Poli Valeria , Camporeale Annalisa TITLE=STAT3-Mediated Metabolic Reprograming in Cellular Transformation and Implications for Drug Resistance JOURNAL=Frontiers in Oncology VOLUME=5 YEAR=2015 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2015.00121 DOI=10.3389/fonc.2015.00121 ISSN=2234-943X ABSTRACT=

Signal transducer and activator of transcription (STAT)3 mediates the signaling downstream of cytokine and growth factor receptors, regulating the expression of target genes. It is constitutively phosphorylated on tyrosine (Y-P) in many tumors, where its transcriptional activity can induce a metabolic switch toward aerobic glycolysis and down-regulate mitochondrial activity, a prominent metabolic feature of most cancer cells, correlating with reduced production of ROS, delayed senescence, and protection from apoptosis. STAT3 can, however, also localize to mitochondria, where its serine-phosphorylated (S-P) form preserves mitochondrial oxidative phosphorylation and controls the opening of the mitochondrial permeability transition pore, also promoting survival and resistance to apoptosis in response to specific signals/oncogenes such as RAS. Thus, downstream of different signals, both nuclear, Y-P STAT3, and mitochondrial, S-P STAT3, can act by promoting cell survival and reducing ROS production. Here, we discuss these properties in the light of potential connections between STAT3-driven alterations of mitochondrial metabolism and the development of drug resistance in cancer patients.