Evidence map›Paper›PMID 30626032›Full record

ArticleCancers2019

Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion.

Flora Guerra, Aurora Paiano, Danilo Migoni, Giulia Girolimetti, Anna Myriam Perrone, Pierandrea De Iaco, Francesco Paolo Fanizzi, Giuseppe Gasparre, Cecilia Bucci

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% of its field
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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  15. Mitochondrial-Derived Vesicles: The Good, the Bad, and the Ugly.International journal of molecular sciences · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Flora GuerraDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. guerraflora@gmail.com.
Aurora PaianoDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. paianoaurora@hotmail.it.
Danilo MigoniDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. danilo.migoni@unisalento.it.
Giulia GirolimettiDepartment of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University Hospital S. Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy. giulsgiuls85@gmail.com.ORCID 0000-0001-8917-3634
Anna Myriam PerroneUnit of Oncologic Gynecology, S. Orsola-Malpighi Hospital, via Massarenti 13, 40138 Bologna, Italy. myriam.perrone@aosp.bo.it.
Pierandrea De IacoUnit of Oncologic Gynecology, S. Orsola-Malpighi Hospital, via Massarenti 13, 40138 Bologna, Italy. pierandrea.deiaco@aosp.bo.it.
Francesco Paolo FanizziDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. francescopaolo.fanizzi@unisalento.it.ORCID 0000-0003-3073-5772
Giuseppe GasparreDepartment of Medical and Surgical Sciences (DIMEC), Medical Genetics Unit, University Hospital S. Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy. giuseppe.gasparre3@unibo.it.
Cecilia BucciDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy. cecilia.bucci@unisalento.it.ORCID 0000-0002-6232-6183
University of Salento · ITIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola · IT

Funding

AIRC (Italian Association for Cancer Research) IG 2016 N. 19068
6 · The paper itself

Abstract

backgroundCisplatin (CDDP) is widely used in treatment of cancer, yet patients often develop resistance with consequent therapeutical failure. In CDDP-resistant cells alterations of endocytosis and lysosomal functionality have been revealed, although their causes and contribution to therapy response are unclear.

methodsWe investigated the role of RAB7A, a key regulator of late endocytic trafficking, in CDDP-resistance by comparing resistant and sensitive cells using western blotting, confocal microscopy and real time PCR. Modulation of RAB7A expression was performed by transfection and RNA interference, while CDDP sensitivity and intracellular accumulation were evaluated by viability assays and chemical approaches, respectively. Also extracellular vesicles were purified and analyzed. Finally, correlations between RAB7A and chemotherapy response was investigated in human patient samples.

resultsWe demonstrated that down-regulation of RAB7A characterizes the chemoresistant phenotype, and that RAB7A depletion increases CDDP-resistance while RAB7A overexpression decreases it. In addition, increased production of extracellular vesicles is modulated by RAB7A expression levels and correlates with reduction of CDDP intracellular accumulation.

conclusionsWe demonstrated, for the first time, that RAB7A regulates CDDP resistance determining alterations in late endocytic trafficking and drug efflux through extracellular vesicles.

Indexed as

chemoresistancecisplatinendocytosislysosomeRAB7A

Identifiers

PMID30626032
PMCPMC6357196
OpenAlexW2909620132

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.