Evidence mapPaperPMID 38947172Full record

ArticleJournal of extracellular biology2024

Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.

Cristóbal Cerda-Troncoso, Felipe Grünenwald, Eloísa Arias-Muñoz, Viviana A Cavieres, Albano Caceres-Verschae, Sergio Hernández, Belén Gaete-Ramírez, Francisca Álvarez-Astudillo, Rodrigo A Acuña, Matias Ostrowski and 2 more

Erratum issuedAbstract read
In one paragraph

Article in Journal of extracellular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Cristóbal Cerda-TroncosoOrganelle Phagy Lab, CEBICEM Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.ORCID https://orcid.org/0000-0002-7573-1997
Felipe GrünenwaldCancer Cell Biology Lab, CEBICEM, Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Eloísa Arias-MuñozOrganelle Phagy Lab, CEBICEM Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Viviana A CavieresOrganelle Phagy Lab, CEBICEM Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Albano Caceres-VerschaeCancer Cell Biology Lab, CEBICEM, Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Sergio HernándezOrganelle Phagy Lab, CEBICEM Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Belén Gaete-RamírezCancer Cell Biology Lab, CEBICEM, Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Francisca Álvarez-AstudilloCancer Cell Biology Lab, CEBICEM, Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.
Rodrigo A AcuñaCentro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana Universidad del Desarrollo Santiago Chile.
Matias OstrowskiFacultad de Medicina, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS) Universidad de Buenos Aires (UBA) Buenos Aires Argentina.
Patricia V BurgosOrganelle Phagy Lab, CEBICEM Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.ORCID https://orcid.org/0000-0003-4521-7978
Manuel Varas-GodoyCancer Cell Biology Lab, CEBICEM, Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Chile.ORCID https://orcid.org/0000-0001-5857-4793

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.

Indexed as

chemo‐EVschemoresistancelysosomal functionovarian cancerRAB27A

Identifiers

PMID38947172
PMCPMC11212338

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.