Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers.
Animals
Antineoplastic Agents
/ pharmacology
Autophagosomes
/ metabolism
Autophagy
/ drug effects
Disease Progression
Endocytosis
/ drug effects
Endosomes
/ metabolism
Exosomes
/ metabolism
Humans
Molecular Targeted Therapy
Neoplasms
/ drug therapy
Proteolysis
Secretory Pathway
/ drug effects
Signal Transduction
/ drug effects
Treatment Outcome
Amphisomes
Autophagy
Autophagy inhibitors
Cancer
Endosomes
Exosomes
Extracellular vesicles
Multivesicular bodies
Non-conventional secretory pathways
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
27 10 2021
27 10 2021
Historique:
received:
01
06
2021
accepted:
11
09
2021
entrez:
28
10
2021
pubmed:
29
10
2021
medline:
25
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34706732
doi: 10.1186/s12943-021-01423-6
pii: 10.1186/s12943-021-01423-6
pmc: PMC8549397
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
140Subventions
Organisme : Grantová Agentura České Republiky
ID : 21-06873S
Organisme : Agentura Pro Zdravotnický Výzkum České Republiky
ID : NU20J-08-00018
Informations de copyright
© 2021. The Author(s).
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