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      Caveolin-1 in the regulation of cell metabolism: a cancer perspective

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          Abstract

          Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and signaling. Recent studies reveal that CAV1 is involved in metabolic alterations – a critical strategy adopted by cancer cells to their survival advantage. Consequently, research findings suggest that CAV1, which is altered in several cancer types, influences tumour development or progression by controlling metabolism. Understanding the molecular interplay between CAV1 and metabolism could help uncover druggable metabolic targets or pathways of clinical relevance in cancer therapy. Here we review from a cancer perspective, the findings that CAV1 modulates cell metabolism with a focus on glycolysis, mitochondrial bioenergetics, glutaminolysis, fatty acid metabolism, and autophagy.

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          Most cited references79

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          On the origin of cancer cells.

          O WARBURG (1956)
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            TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

            The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
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              The role of autophagy in cancer development and response to therapy.

              Autophagy is a process in which subcellular membranes undergo dynamic morphological changes that lead to the degradation of cellular proteins and cytoplasmic organelles. This process is an important cellular response to stress or starvation. Many studies have shed light on the importance of autophagy in cancer, but it is still unclear whether autophagy suppresses tumorigenesis or provides cancer cells with a rescue mechanism under unfavourable conditions. What is the present state of our knowledge about the role of autophagy in cancer development, and in response to therapy? And how can the autophagic process be manipulated to improve anticancer therapeutics?
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                Author and article information

                Contributors
                christoph.meyer@medma.uni-heidelberg.de
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                16 November 2016
                16 November 2016
                2016
                : 15
                : 71
                Affiliations
                [1 ]Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68167 Germany
                [2 ]Molecular Hepatology Section, Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68167 Germany
                Article
                558
                10.1186/s12943-016-0558-7
                5112640
                27852311
                65faaf3a-cfaf-4538-aa63-5b0527ae91cd
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 August 2016
                : 3 November 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: Do373/13-1
                Award ID: Me4532/1-1
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: PTJ-FKZ: 031L0043
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004963, Seventh Framework Programme;
                Award ID: PITN-GA-2012-316549
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                cav1,glycolysis,glutaminolysis,mitochondrion,fatty acid metabolism,autophagy,metabolic targets

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