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

J 2021

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

RAUDENSKÁ, Martina, Jan BALVAN and Michal MASAŘÍK

Basic information

Original name

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

Authors

RAUDENSKÁ, Martina (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution) and Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Molecular Cancer, LONDON, BioMed Central, 2021, 1476-4598

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 41.444

RIV identification code

RIV/00216224:14110/21:00119418

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s12943-021-01423-6

UT WoS

000712572400001

Keywords in English

Autophagy; Autophagy inhibitors; Cancer; Endosomes; Multivesicular bodies; Extracellular vesicles; Exosomes; Amphisomes; Non-conventional secretory pathways

Abstract

V originále

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.

Links

GA21-06873S, research and development project

Name: Metabolická symbióza mezi nádorovými buňkami a fibroblasty asociovaných s nádorem u nádorů v oblasti hlavy a krku

Investor: Czech Science Foundation

MUNI/A/1246/2020, interní kód MU

Name: Kardiovaskulární systém: od iontového kanálu k celotělovému modelu (Acronym: KAVASYKAMO)

Investor: Masaryk University

MUNI/A/1698/2020, interní kód MU

Name: Od molekulární, buněčné a tkáňové k systémové patofyziologii vybraných komplexních nemocí (Acronym: ComplexPF)

Investor: Masaryk University

NU20J-08-00018, research and development project

Name: Exosomální RNA produkovaná fibroblasty asociovanými s nádorem jako relevantní marker v prognóze nádorů hlavy a krku

Investor: Ministry of Health of the CR, Subprogram 2 - junior

Citovat

RAUDENSKÁ, Martina, Jan BALVAN and Michal MASAŘÍK. Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers. Molecular Cancer. LONDON: BioMed Central, 2021, vol. 20, No 1, p. 1-27. ISSN 1476-4598. Available from: https://dx.doi.org/10.1186/s12943-021-01423-6.

@article{1809523,
   author = {Raudenská, Martina and Balvan, Jan and Masařík, Michal},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s12943-021-01423-6},
   keywords = {Autophagy; Autophagy inhibitors; Cancer; Endosomes; Multivesicular bodies; Extracellular vesicles; Exosomes; Amphisomes; Non-conventional secretory pathways},
   language = {eng},
   issn = {1476-4598},
   journal = {Molecular Cancer},
   title = {Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers},
   url = {https://molecular-cancer.biomedcentral.com/track/pdf/10.1186/s12943-021-01423-6.pdf},
   volume = {20},
   year = {2021}
}

TY  - JOUR
ID  - 1809523
AU  - Raudenská, Martina - Balvan, Jan - Masařík, Michal
PY  - 2021
TI  - Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers
JF  - Molecular Cancer
VL  - 20
IS  - 1
SP  - 1-27
EP  - 1-27
PB  - BioMed Central
SN  - 14764598
KW  - Autophagy
KW  - Autophagy inhibitors
KW  - Cancer
KW  - Endosomes
KW  - Multivesicular bodies
KW  - Extracellular vesicles
KW  - Exosomes
KW  - Amphisomes
KW  - Non-conventional secretory pathways
UR  - https://molecular-cancer.biomedcentral.com/track/pdf/10.1186/s12943-021-01423-6.pdf
N2  - 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.
ER  -

RAUDENSKÁ, Martina, Jan BALVAN and Michal MASAŘÍK. Crosstalk between autophagy inhibitors and endosome-related secretory pathways: a challenge for autophagy-based treatment of solid cancers. \textit{Molecular Cancer}. LONDON: BioMed Central, 2021, vol.~20, No~1, p.~1-27. ISSN~1476-4598. Available from: https://dx.doi.org/10.1186/s12943-021-01423-6.

Detailed Information on Publication Record