Evidence map›Paper›PMID 32789331›Full record

ArticleMetallomics : integrated biometal science2020

A recombinant platform to characterize the role of transmembrane protein hTMEM205 in Pt(II)-drug resistance and extrusion.

Marc J Gallenito, Tahir S Qasim, Jasmine N Tutol, Ved Prakash, Sheel C Dodani, Gabriele Meloni

Open access · bronzeAbstract read
In one paragraph

Article in Metallomics : integrated biometal science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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

6 authors at 1 institution in 1 country.

Marc J GallenitoDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA. gabriele.meloni@utdallas.edu.ORCID 0000-0002-5096-724X
Tahir S QasimDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA. gabriele.meloni@utdallas.edu.ORCID 0000-0003-3521-1900
Jasmine N TutolDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA. gabriele.meloni@utdallas.edu.ORCID 0000-0001-8493-4203
Ved PrakashImaging and Histology Core and Olympus Discovery Center, Office of Research, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0000-0002-1172-5969
Sheel C DodaniDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA. gabriele.meloni@utdallas.edu.ORCID 0000-0003-0271-6080
Gabriele MeloniDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA. gabriele.meloni@utdallas.edu.ORCID 0000-0003-4976-1401
The University of Texas at Dallas · US

Funding

Principles of selectivity and translocation in transition metal transporters, metallochaperones, and associated metalloproteinsR35GM128704 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI Gabriele Meloni · 2018 to 2026
$3.5M
Optical Imaging Tools for Elucidating the Roles of Anions and Anionic Modifications in Cellular SignalingR35GM128923 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI Sheel Dodani · 2018 to 2026
$3.4M
DO HIGH DOSE B VITAMINS DELAY AGE-RELATED DECAYR21AT001918 · NCCIH · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI AMES, BRUCE N · 2004 to 2005
$400k
NCCIH NIH HHS R21 AT001918NIGMS NIH HHS R35 GM128704NIGMS NIH HHS R35 GM128923
6 · The paper itself

Abstract

Platinum-coordination complexes are among the most effective chemotherapeutic drugs used in clinics for the treatment of cancer. Despite their efficacy, cancer cells can develop drug resistance leading to treatment failure and relapse. Cellular uptake and extrusion of Pt(ii)-complexes mediated by transmembrane proteins are critical in controlling the intracellular concentration of Pt(ii)-drugs and in developing pre-target resistance. TMEM205 is a human transmembrane protein (hTMEM205) overexpressed in cancer cells that are resistant to cisplatin, but its molecular function underlying - resistance remains elusive. We developed a low-cost and high-throughput recombinant expression platform coupled to in vivo functional resistance assays to study the molecular mechanism by which the orphan hTMEM205 protects against Pt(ii)-complex toxicity. Based on the original observation by the Rosenberg group, which led to the discovery of cisplatin, we performed quantitative analysis of the effects of Pt(ii)-coordination complexes on cellular growth and filamentation in E. coli cells expressing hTMEM205. By coupling our methods with Pt quantification and cellular profiling in control and hTMEM205-expressing cells, we demonstrate that hTMEM205 mediates Pt(ii)-drug export selectively towards cisplatin and oxaliplatin but not carboplatin. By mutation analysis, we reveal that hTMEM205 recognizes and allows Pt(ii)-extrusion by a putative sulfur-based translocation mechanism, thereby resulting in pre-target resistance. Thus, hTMEM205 represents a new potential target that can be exploited to reduce cellular resistance towards Pt(ii)-drugs.

Indexed as

Antineoplastic AgentsBiological TransportCisplatinCoordination ComplexesDrug Resistance, NeoplasmEscherichia coliGene ExpressionHumansMembrane ProteinsMutationNeoplasmsOrganoplatinum CompoundsOxaliplatinRecombinant ProteinsAntineoplastic AgentsCisplatinCoordination ComplexesMembrane ProteinsOrganoplatinum CompoundsOxaliplatinRecombinant ProteinsTMEM205 protein, human

Identifiers

PMID32789331
PMCPMC7578072
OpenAlexW3042613738

What OpenQuestion holds

Textmetadata
LicenceTDM
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.