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      Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer

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          Abstract

          Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.

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          Cancer-related inflammation.

          Alberto Mantovani, Paola Allavena, Antonio Sica … (2008)
          The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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            Tumor-associated macrophages: from mechanisms to therapy.

            Roy Noy, Jeffrey W Pollard (2014)
            The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate that these macrophages generally play a protumoral role. In the primary tumor, macrophages can stimulate angiogenesis and enhance tumor cell invasion, motility, and intravasation. During monocytes and/or metastasis, macrophages prime the premetastatic site and promote tumor cell extravasation, survival, and persistent growth. Macrophages are also immunosuppressive, preventing tumor cell attack by natural killer and T cells during tumor progression and after recovery from chemo- or immunotherapy. Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Sphingolipids and their metabolism in physiology and disease

              Yusuf Hannun, Lina M. Obeid (2017)
              Studies of bioactive lipids in general and sphingolipids in particular have intensified over the past several years, revealing an unprecedented and unanticipated complexity of the lipidome and its many functions, which rivals, if not exceeds, that of the genome or proteome. These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingolipid metabolism to key human diseases. Nevertheless, the fairly nascent field of bioactive sphingolipids still faces challenges in its biochemical and molecular underpinnings, including defining the molecular mechanisms of pathway and enzyme regulation, the study of lipid-protein interactions and the development of cellular probes, suitable biomarkers and therapeutic approaches.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 13 January 2021
                Publication date Collection: January 2021
                Volume: 22
                Issue: 2
                Electronic Location Identifier: 726
                Affiliations
                [1 ]Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy; michela.codini@ 123456unipg.it
                [2 ]Department of Biology, University of Pisa, 56127 Pisa, Italy; mercedes.garcia@ 123456unipi.it
                [3 ]Interdepartmental Research Center Nutrafood, Nutraceuticals and Food for Health, University of Pisa, 56127 Pisa, Italy
                Author notes
                [* ]Correspondence: elisabetta.albi@ 123456unipg.it ; Tel./Fax: +39-0755857940
                Author information
                https://orcid.org/0000-0002-1562-4495
                https://orcid.org/0000-0002-1344-2786
                https://orcid.org/0000-0002-5745-5343
                Article
                Publisher ID: ijms-22-00726
                DOI: 10.3390/ijms22020726
                PMC ID: 7828315
                PubMed ID: 33450869
                SO-VID: 320c271b-2a4a-45a9-ae96-d3c5414b5bf1
                Copyright © © 2021 by the authors.
                License:

                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/).

                History
                Date received : 15 December 2020
                Date accepted : 11 January 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: cholesterol,sphingolipid,cancer,lipid raft,therapeutic target
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: cholesterol, sphingolipid, cancer, lipid raft, therapeutic target

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