STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications

The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is activated constitutively in a wide array of human cancers. It is an appealing molecular target for novel therapy as it directly regulates expression of genes involved in cell proliferation, survival, ang...

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Autores principales:	Isidora Tošić, David A. Frank
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	STAT3 transcription factor Protein processing, Post-translational Adenosine triphosphate Lipid metabolism Metabolism Neoplasms Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bcd24241ef74472dafa6987a998b7cf9
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spelling	oai:doaj.org-article:bcd24241ef74472dafa6987a998b7cf92021-11-30T04:14:36ZSTAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications1476-558610.1016/j.neo.2021.10.003https://doaj.org/article/bcd24241ef74472dafa6987a998b7cf92021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621000889https://doaj.org/toc/1476-5586The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is activated constitutively in a wide array of human cancers. It is an appealing molecular target for novel therapy as it directly regulates expression of genes involved in cell proliferation, survival, angiogenesis, chemoresistance and immune responsiveness. In addition to these well-established oncogenic roles, STAT3 has also been found to mediate a wide array of functions in modulating cellular behavior. The transcriptional function of STAT3 is canonically regulated through tyrosine phosphorylation. However, STAT3 phosphorylated at a single serine residue can allow incorporation of this protein into the inner mitochondrial membrane to support oxidative phosphorylation (OXPHOS) and maximize the utility of glucose sources. Conflictingly, its canonical transcriptional activity suppresses OXPHOS and favors aerobic glycolysis to promote oncogenic behavior. Apart from mediating the energy metabolism and controversial effects on ATP production, STAT3 signaling modulates lipid metabolism of cancer cells. By mediating fatty acid synthesis and beta oxidation, STAT3 promotes employment of available resources and supports survival in the conditions of metabolic stress. Thus, the functions of STAT3 extend beyond regulation of oncogenic genes expression to pleiotropic effects on a spectrum of essential cellular processes. In this review, we dissect the current knowledge on activity and mechanisms of STAT3 involvement in transcriptional regulation, mitochondrial function, energy production and lipid metabolism of malignant cells, and its implications to cancer pathogenesis and therapy.Isidora TošićDavid A. FrankElsevierarticleSTAT3 transcription factorProtein processing, Post-translationalAdenosine triphosphateLipid metabolismMetabolismNeoplasmsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1167-1178 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	STAT3 transcription factor Protein processing, Post-translational Adenosine triphosphate Lipid metabolism Metabolism Neoplasms Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	STAT3 transcription factor Protein processing, Post-translational Adenosine triphosphate Lipid metabolism Metabolism Neoplasms Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Isidora Tošić David A. Frank STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
description	The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is activated constitutively in a wide array of human cancers. It is an appealing molecular target for novel therapy as it directly regulates expression of genes involved in cell proliferation, survival, angiogenesis, chemoresistance and immune responsiveness. In addition to these well-established oncogenic roles, STAT3 has also been found to mediate a wide array of functions in modulating cellular behavior. The transcriptional function of STAT3 is canonically regulated through tyrosine phosphorylation. However, STAT3 phosphorylated at a single serine residue can allow incorporation of this protein into the inner mitochondrial membrane to support oxidative phosphorylation (OXPHOS) and maximize the utility of glucose sources. Conflictingly, its canonical transcriptional activity suppresses OXPHOS and favors aerobic glycolysis to promote oncogenic behavior. Apart from mediating the energy metabolism and controversial effects on ATP production, STAT3 signaling modulates lipid metabolism of cancer cells. By mediating fatty acid synthesis and beta oxidation, STAT3 promotes employment of available resources and supports survival in the conditions of metabolic stress. Thus, the functions of STAT3 extend beyond regulation of oncogenic genes expression to pleiotropic effects on a spectrum of essential cellular processes. In this review, we dissect the current knowledge on activity and mechanisms of STAT3 involvement in transcriptional regulation, mitochondrial function, energy production and lipid metabolism of malignant cells, and its implications to cancer pathogenesis and therapy.
format	article
author	Isidora Tošić David A. Frank
author_facet	Isidora Tošić David A. Frank
author_sort	Isidora Tošić
title	STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
title_short	STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
title_full	STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
title_fullStr	STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
title_full_unstemmed	STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications
title_sort	stat3 as a mediator of oncogenic cellular metabolism: pathogenic and therapeutic implications
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bcd24241ef74472dafa6987a998b7cf9
work_keys_str_mv	AT isidoratosic stat3asamediatorofoncogeniccellularmetabolismpathogenicandtherapeuticimplications AT davidafrank stat3asamediatorofoncogeniccellularmetabolismpathogenicandtherapeuticimplications
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STAT3 as a mediator of oncogenic cellular metabolism: Pathogenic and therapeutic implications

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