Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers


Posted: 2021-10-28 19:00:00
Review Mol Cancer . 2021 Oct 27;20(1):140. doi: 10.1186/s12943-021-01423-6. Affiliations Expand Affiliations 1 Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. 2 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic. 3 Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. 4 Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. masarik@med.muni.cz. 5 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic. masarik@med.muni.cz. 6 Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. masarik@med.muni.cz. 7 BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50, Vestec, Czech Republic. masarik@med.muni.cz. 8 Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology in Prague, Technická 5, CZ-166 28, Prague, Czech Republic. masarik@med.muni.cz. # Contributed equally. Item in Clipboard Review Martina Raudenska et al. Mol Cancer. 2021. Show details Display options Display options Format Mol Cancer . 2021 Oct 27;20(1):140. doi: 10.1186/s12943-021-01423-6. Affiliations 1 Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. 2 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic. 3 Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. 4 Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. masarik@med.muni.cz. 5 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic. masarik@med.muni.cz. 6 Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic. masarik@med.muni.cz. 7 BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50, Vestec, Czech Republic. masarik@med.muni.cz. 8 Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology in Prague, Technická 5, CZ-166 28, Prague, Czech Republic. masarik@med.muni.cz. # Contributed equally. Item in Clipboard CiteDisplay options Display options Format Abstract Autophagy is best known for its role in organelle and protein turnover, cell quality control, and metabolism. The autophagic machinery has, however, also adapted to enable protein trafficking and unconventional secretory pathways so that organelles (such as autophagosomes and multivesicular bodies) delivering cargo to lysosomes for degradation can change their mission from fusion with lysosomes to fusion with the plasma membrane, followed by secretion of the cargo from the cell. Some factors with key signalling functions do not enter the conventional secretory pathway but can be secreted in an autophagy-mediated manner.Positive clinical results of some autophagy inhibitors are encouraging. Nevertheless, it is becoming clear that autophagy inhibition, even within the same cancer type, can affect cancer progression differently. Even next-generation inhibitors of autophagy can have significant non-specific effects, such as impacts on endosome-related secretory pathways and secretion of extracellular vesicles (EVs). Many studies suggest that cancer cells release higher amounts of EVs compared to non-malignant cells, which makes the effect of autophagy inhibitors on EVs secretion highly important and attractive for anticancer therapy. In this review article, we discuss how different inhibitors of autophagy may influence the secretion of EVs and summarize the non-specific effects of autophagy inhibitors with a focus on endosome-related secretory pathways. Modulation of autophagy significantly impacts not only the quantity of EVs but also their content, which can have a deep impact on the resulting pro-tumourigenic or anticancer effect of autophagy inhibitors used in the antineoplastic treatment of solid cancers. Keywords: Amphisomes; Autophagy; Autophagy inhibitors; Cancer; Endosomes; Exosomes; Extracellular vesicles; Multivesicular bodies; Non-conventional secretory pathways. © 2021. The Author(s). References Mizushima N. Physiological functions of autophagy. Curr Top Microbiol Immunol. 2009;335:71–84. - PubMed - PMC Clarke AJ, Simon AK. Autophagy in the renewal, differentiation and homeostasis of immune cells. Nat Rev Immunol. 2019;19(3):170–83. - PubMed - DOI - PMC Deretic V, Jiang S, Dupont N. Autophagy intersections with conventional and unconventional secretion in tissue development, remodeling and inflammation. Trends Cell Biol. 2012;22(8):397–406. - PubMed - PMC - DOI Salimi L, et al. Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells. Cell Biosci. 2020;10(1):64. - PubMed - PMC - DOI Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. 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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
6月 20, 2019 バイオアソシエイツ

移植幹細胞由来エクソソームは心臓発作からの回復を助ける。移植細胞からの循環エキソソーム解析(液体生検)は医師が回復の程度を把握することを可能にする。

心筋の強化や他の疾患を治療する幹細胞療法は、ヒト臨床試験で有望視され始めている。 しかし、臨床成果の観察以外に、標的臓器内の移植細胞の有効性を評価するうえで再現性の欠如や使用期限、非侵襲的なツールの欠如は、幹細胞分野の進歩を遅らせてきた。 メリーランド大学医学部(UMSOM)、ペンシルバニア大学、およびエモリー大学の研究者らは、移植された幹細胞の有効性を追跡するのに血液検査が使用できると理論づけた。 彼らは、移植幹細胞からレシピエントの血液に分泌される エクソソーム と呼ばれる微小な細胞成分を分析した。…

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