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      Desmoglein-2 as a cancer modulator: friend or foe?

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          Abstract

          Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer.

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          GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis

          Abstract Introduced in 2017, the GEPIA (Gene Expression Profiling Interactive Analysis) web server has been a valuable and highly cited resource for gene expression analysis based on tumor and normal samples from the TCGA and the GTEx databases. Here, we present GEPIA2, an updated and enhanced version to provide insights with higher resolution and more functionalities. Featuring 198 619 isoforms and 84 cancer subtypes, GEPIA2 has extended gene expression quantification from the gene level to the transcript level, and supports analysis of a specific cancer subtype, and comparison between subtypes. In addition, GEPIA2 has adopted new analysis techniques of gene signature quantification inspired by single-cell sequencing studies, and provides customized analysis where users can upload their own RNA-seq data and compare them with TCGA and GTEx samples. We also offer an API for batch process and easy retrieval of the analysis results. The updated web server is publicly accessible at http://gepia2.cancer-pku.cn/.
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            Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

            The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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              Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

              Tumor-derived exosomes (TDEs) participate in formation and progression of different cancer processes, including tumor microenvironment (TME) remodeling, angiogenesis, invasion, metastasis and drug-resistance. Exosomes initiate or suppress various signaling pathways in the recipient cells via transmitting heterogeneous cargoes. In this review we discuss exosome biogenesis, exosome mediated metastasis and chemoresistance. Furthermore, tumor derived exosomes role in tumor microenvironment remodeling, and angiogenesis is reviewed. Also, exosome induction of epithelial mesenchymal transition (EMT) is highlighted. More importantly, we discuss extensively how exosomes regulate drug resistance in several cancers. Thus, understanding exosome biogenesis, their contents and the molecular mechanisms and signaling pathways that are responsible for metastasis and drug-resistance mediated by TDEs may help to devise novel therapeutic approaches for cancer progression particularly to overcome therapy-resistance and preventing metastasis as major factors of cancer mortality. Electronic supplementary material The online version of this article (10.1186/s12943-019-0991-5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2541180Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2577635Role: Role: Role:
                Role: Role:
                Role:
                Role:
                URI : https://loop.frontiersin.org/people/476963Role:
                URI : https://loop.frontiersin.org/people/1655009Role:
                URI : https://loop.frontiersin.org/people/2579837Role: Role:
                URI : https://loop.frontiersin.org/people/702170Role: Role:
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                22 December 2023
                2023
                : 13
                : 1327478
                Affiliations
                [1] 1 Centre for Cancer Biology, SA Pathology and the University of South Australia , Adelaide, SA, Australia
                [2] 2 Adelaide Medical School, University of Adelaide , Adelaide, SA, Australia
                [3] 3 Basil Hetzel Institute, Queen Elizabeth Hospital, SA , Adelaide, Australia
                [4] 4 Royal Adelaide Hospital , Adelaide, SA, Australia
                [5] 5 Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University , Philadelphia, PA, United States
                Author notes

                Edited by: Peng Su, Shandong University, China

                Reviewed by: Nagaraja Sethuraman Balakathiresan, National Institute on Alcohol Abuse and Alcoholism (NIH), United States

                Jian Li, Mianyang Third People’s Hospital, China

                *Correspondence: Claudine S. Bonder, claudine.bonder@ 123456unisa.edu.au

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fonc.2023.1327478
                10766750
                38188287
                75742652-6bd3-4f4f-96c9-0945eff88a25
                Copyright © 2023 Myo Min, Ffrench, McClure, Ortiz, Dorward, Samuel, Ebert, Mahoney and Bonder

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 October 2023
                : 04 December 2023
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 145, Pages: 15, Words: 6085
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This review was supported by grants to CB: a Tour de Cure (Pioneering Grant RSP-358-2020), Cancer Council SA (Beat Cancer Project Support GNT2013221) and NHMRC (GNT2021009 & GNT2013460). KM, CF and MO were supported by a RTP/USAPA post-graduate scholarship. CF was also supported by the Australian Rotary Health and Phillip & Glenis Hayes PhD scholarship.
                Categories
                Oncology
                Review
                Custom metadata
                Cancer Molecular Targets and Therapeutics

                Oncology & Radiotherapy
                desmoglein-2 (dsg2),cancer,cadherin,intercellular junctions,prognostic biomarker,vasculogenic mimicry,non-canonical role

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