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oai:recercat.cat:11351/101042025-10-24T08:57:07Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

Endocytic trafficking of connexins in cancer pathogenesis Totland, Max Zachrisson Omori, Yasufumi Sørensen, Vigdis Kryeziu, Kushtrim Brech, Andreas Aasen, Trond Institut Català de la Salut [Totland MZ, Kryeziu K] Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. [Omori Y] Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, Japan. [Sørensen V] Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. [Aasen T] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Brech A] Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway. Section for Physiology and Cell Biology, Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway Vall d'Hebron Barcelona Hospital Campus Càncer Connexines - Metabolisme Unions gap (Biologia cel·lular) DISEASES::Neoplasms ANATOMY::Cells::Cellular Structures::Cell Membrane::Cell Membrane Structures::Intercellular Junctions::Gap Junctions CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Transport Proteins::Connexins ENFERMEDADES::neoplasias ANATOMÍA::células::estructuras celulares::membrana celular::estructuras de la membrana celular::uniones intercelulares::uniones comunicantes COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::proteínas de transporte de membrana::conexinas Cancer; Connexin; Ubiquitin Càncer; Connexina; Ubiquitina Cáncer; Conexina; Ubiquitina Gap junctions are specialized regions of the plasma membrane containing clusters of channels that provide for the diffusion of ions and small molecules between adjacent cells. A fundamental role of gap junctions is to coordinate the functions of cells in tissues. Cancer pathogenesis is usually associated with loss of intercellular communication mediated by gap junctions, which may affect tumor growth and the response to radio- and chemotherapy. Gap junction channels consist of integral membrane proteins termed connexins. In addition to their canonical roles in cell-cell communication, connexins modulate a range of signal transduction pathways via interactions with proteins such as β-catenin, c-Src, and PTEN. Consequently, connexins can regulate cellular processes such as cell growth, migration, and differentiation through both channel-dependent and independent mechanisms. Gap junctions are dynamic plasma membrane entities, and by modulating the rate at which connexins undergo endocytosis and sorting to lysosomes for degradation, cells can rapidly adjust the level of gap junctions in response to alterations in the intracellular or extracellular milieu. Current experimental evidence indicates that aberrant trafficking of connexins in the endocytic system is intrinsically involved in mediating the loss of gap junctions during carcinogenesis. This review highlights the role played by the endocytic system in controlling connexin degradation, and consequently gap junction levels, and discusses how dysregulation of these processes contributes to the loss of gap junctions during cancer development. We also discuss the therapeutic implications of aberrant endocytic trafficking of connexins in cancer cells. E. Leithe acknowledges funding from the South-Eastern Norway Regional Health Authority (grant number 2016013) and the Kristian Gerhard Jebsen Foundation. T. Aasen acknowledges funding from Instituto de Salud Carlos III, grant PI21/00470 co-financed by the European Regional Development Fund (ERDF). 2023-08-21T09:46:08Z 2023-08-21T09:46:08Z 2023-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Totland MZ, Omori Y, Sørensen V, Kryeziu K, Aasen T, Brech A, et al. Endocytic trafficking of connexins in cancer pathogenesis. Biochim Biophys Acta - Mol Basis Dis. 2023 Oct;1869(7):166812. 0925-4439 https://hdl.handle.net/11351/10104 10.1016/j.bbadis.2023.166812 37454772 http://hdl.handle.net/11351/10104 eng Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease;1869(7) https://doi.org/10.1016/j.bbadis.2023.166812 info:eu-repo/grantAgreement/ES/PE2017-2020/PI21%2F00470 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia