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Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases

An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA),...

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Autores principales: Fazio, Antonietta, Owusu Obeng, Eric, Rusciano, Isabella, Marvi, Maria Vittoria, Zoli, Matteo, Mongiorgi, Sara, Ramazzotti, Giulia, Follo, Matilde Yung, McCubrey, James A., Cocco, Lucio, Manzoli, Lucia, Ratti, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432101/
https://www.ncbi.nlm.nih.gov/pubmed/32722576
http://dx.doi.org/10.3390/ijms21155297
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author Fazio, Antonietta
Owusu Obeng, Eric
Rusciano, Isabella
Marvi, Maria Vittoria
Zoli, Matteo
Mongiorgi, Sara
Ramazzotti, Giulia
Follo, Matilde Yung
McCubrey, James A.
Cocco, Lucio
Manzoli, Lucia
Ratti, Stefano
author_facet Fazio, Antonietta
Owusu Obeng, Eric
Rusciano, Isabella
Marvi, Maria Vittoria
Zoli, Matteo
Mongiorgi, Sara
Ramazzotti, Giulia
Follo, Matilde Yung
McCubrey, James A.
Cocco, Lucio
Manzoli, Lucia
Ratti, Stefano
author_sort Fazio, Antonietta
collection PubMed
description An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA.
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spelling pubmed-74321012020-08-24 Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases Fazio, Antonietta Owusu Obeng, Eric Rusciano, Isabella Marvi, Maria Vittoria Zoli, Matteo Mongiorgi, Sara Ramazzotti, Giulia Follo, Matilde Yung McCubrey, James A. Cocco, Lucio Manzoli, Lucia Ratti, Stefano Int J Mol Sci Review An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA. MDPI 2020-07-26 /pmc/articles/PMC7432101/ /pubmed/32722576 http://dx.doi.org/10.3390/ijms21155297 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fazio, Antonietta
Owusu Obeng, Eric
Rusciano, Isabella
Marvi, Maria Vittoria
Zoli, Matteo
Mongiorgi, Sara
Ramazzotti, Giulia
Follo, Matilde Yung
McCubrey, James A.
Cocco, Lucio
Manzoli, Lucia
Ratti, Stefano
Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title_full Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title_fullStr Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title_full_unstemmed Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title_short Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
title_sort subcellular localization relevance and cancer-associated mechanisms of diacylglycerol kinases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432101/
https://www.ncbi.nlm.nih.gov/pubmed/32722576
http://dx.doi.org/10.3390/ijms21155297
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