Subsequently, these complexes recruit the apoptosis-linked gene 2–interacting protein X (ALIX), which aids in recruiting the ESCRT-III complex containing proteins involved in vesicle budding and the release from the plasma membrane. ESCRT-0, ESCRT-I, and ESCRT-II are held responsible for the binding, through the tumor susceptibility gene 101 (TSG101), of specific cargoes selecting ubiquitinated proteins and segregating them into microdomains found on the endosomal membrane. These proteins have been described to select ubiquitinated proteins and segregate them into microdomains found on the endosomal membrane. The first mechanism requires the presence of endosomal sorting complexes required for transport (ESCRT) complex members ( 8). The three main mechanisms of ILV formation are described. As a next step, these ILV-containing MVBs can either be redirected to degradation in the lysosome or fused with the plasma membrane (PM), thus leading to the release of exosomes. Small EVs are nano-sized vesicles smaller than 150 nm, which originate from intraluminal vesicles (ILVs) through the formation of multivesicular bodies (MVBs) ( 7). EVs can be classified into three different subtypes according to their size, biophysical properties, and biogenesis: small EVs (exosomes), medium EVs (microvesicles), and apoptotic bodies ( 6) ( Figure 1). EVs are recently recognized as mediators of communication due to their molecular cargo consisting of biomolecules (lipids, nucleic acids, carbohydrates, and proteins) transferable to neighboring cells ( 3– 5). In this review, we resume the main body of knowledge supporting the crucial role of EVs in the context of chemoresistance, with a particular emphasis on the mechanisms related to some of the main drugs used to fight cancer.Įxtracellular vesicles (EVs) are a heterogeneous population of double membrane-enclosed lipidic structures, which are actively secreted by eukaryotic and prokaryotic cells ( 1, 2). Extracellular v esicles (EVs) can directly transfer or epigenetically induce to a target cell the molecular machinery responsible for the acquisition of resistance to drugs. The main mechanisms reported are the expression of transporter proteins, the induction or mutations of oncogenes and transcription factors, the alteration in genomic or mitochondrial DNA, the triggering of autophagy or epithelial-to-mesenchymal transition, the acquisition of a stem phenotype, and the activation of tumor microenvironment cells. Many pathways have been elucidated to trigger insensitiveness to drugs, generally associated with the promotion of tumor growth, aggressiveness, and metastatisation. Chemoresistance is tightly linked to these features and is mainly responsible for the failure of cancer eradication, leaving patients without a crucial medical strategy. Recurrence and metastatization dampen the patients’ overall survival after the first diagnosis nevertheless, the large knowledge of the molecular bases drives these aspects. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyĪlthough surgical procedures and clinical care allow reaching high success in fighting most tumors, cancer is still a formidable foe.Simona Pompili †, Antonella Vetuschi †, Roberta Sferra ‡ and Alfredo Cappariello *‡
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |