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      Perturbing the Dynamics and Organization of Cell Membrane Components: A New Paradigm for Cancer-Targeted Therapies

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          Abstract

          Cancer is a multi-process disease where different mechanisms exist in parallel to ensure cell survival and constant adaptation to the extracellular environment. To adapt rapidly, cancer cells re-arrange their plasma membranes to sustain proliferation, avoid apoptosis and resist anticancer drugs. In this review, we discuss novel approaches based on the modifications and manipulations that new classes of molecules can exert in the plasma membrane lateral organization and order of cancer cells, affecting growth factor signaling, invasiveness, and drug resistance. Furthermore, we present azurin, an anticancer protein from bacterial origin, as a new approach in the development of therapeutic strategies that target the cell membrane to improve the existing standard therapies.

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          Most cited references88

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          Caveolae as plasma membrane sensors, protectors and organizers.

          Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types. The past few years have seen a quantum leap in our understanding of the formation, dynamics and functions of these enigmatic structures. Caveolae have now emerged as vital plasma membrane sensors that can respond to plasma membrane stresses and remodel the extracellular environment. Caveolae at the plasma membrane can be removed by endocytosis to regulate their surface density or can be disassembled and their structural components degraded. Coat proteins, called cavins, work together with caveolins to regulate the formation of caveolae but also have the potential to dynamically transmit signals that originate in caveolae to various cellular destinations. The importance of caveolae as protective elements in the plasma membrane, and as membrane organizers and sensors, is highlighted by links between caveolae dysfunction and human diseases, including muscular dystrophies and cancer.
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            ABC transporters in cancer: more than just drug efflux pumps.

            Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. However, a considerable body of evidence also points to their importance in cancer extending beyond drug transport to fundamental roles in tumour biology. Currently, much of the evidence for these additional roles is correlative and definitive studies are needed to confirm causality. We propose that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
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              Biological activities and distribution of plant saponins.

              Plant saponins are widely distributed amongst plants and have a wide range of biological properties. The more recent investigations and findings into their biological activities were summarized. Isolation studies of saponins were examined to determine which are the more commonly studied plant families and in which families saponins have been identified.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                04 December 2018
                December 2018
                : 19
                : 12
                : 3871
                Affiliations
                [1 ]iBB-Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal
                [2 ]Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, 1049-001 Lisbon, Portugal
                Author notes
                [* ]Correspondence: nuno.bernardes@ 123456tecnico.ulisboa.pt (N.B.); afialho@ 123456tecnico.ulisboa.pt (A.M.F.); Tel.: +351-21-8417684 (IST)
                Author information
                https://orcid.org/0000-0002-4495-6608
                https://orcid.org/0000-0002-8066-5787
                Article
                ijms-19-03871
                10.3390/ijms19123871
                6321595
                30518103
                070e5e60-3c36-4638-ae05-742c4d895a20
                © 2018 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/).

                History
                : 04 October 2018
                : 03 December 2018
                Categories
                Review

                Molecular biology
                membrane targeted therapy,membrane rafts,cancer therapy,azurin,membrane modulation

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