Evidence map›Paper›PMID 26220590›Full record

ArticleOncotarget2015

3'-Phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes non-small cell lung cancer cells to DNA damaging agents.

Ada W Y Leung, Wieslawa H Dragowska, Daniel Ricaurte, Brian Kwok, Veena Mathew, Jeroen Roosendaal, Amith Ahluwalia, Corinna Warburton, Janessa J Laskin, Peter C Stirling and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. 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

12 authors at 5 institutions in 2 countries.

Ada W Y LeungExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Wieslawa H DragowskaExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Daniel RicaurteExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Brian KwokExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Veena MathewTerry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Jeroen RoosendaalExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Amith AhluwaliaExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Corinna WarburtonExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Janessa J LaskinMedical Oncology, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Peter C StirlingTerry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Mohammed A QadirExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Marcel B BallyExperimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
BC Cancer Agency · CAUniversity of British Columbia · CACentre for Drug Research and Development · CATerry Fox Research Institute · CAUtrecht University · NL

Funding

Canadian Institutes of Health Research MOP 89948
6 · The paper itself

Abstract

Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known driver mutation is platinum-based chemotherapy, which has a response rate of only 30-33%. Through an siRNA screen, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces clonogenicity of NSCLC cells by 98.7% (p < 0.001), increases DNA damage, and induces G1/S phase cell cycle arrest and apoptosis. PAPSS1 silencing also sensitized NSCLC cells to other DNA crosslinking agents, radiation, and topoisomerase I inhibitors, but not topoisomerase II inhibitors. Chemo-sensitization was not observed in normal epithelial cells. Knocking out the PAPSS1 homolog did not sensitize yeast to cisplatin, suggesting that sulfate bioavailability for amino acid synthesis is not the cause of sensitization to DNA damaging agents. Rather, sensitization may be due to sulfation reactions involved in blocking the action of DNA damaging agents, facilitating DNA repair, promoting cancer cell survival under therapeutic stress or reducing the bioavailability of DNA damaging agents. Our study demonstrates for the first time that PAPSS1 could be targeted to improve the activity of multiple anticancer agents used to treat NSCLC.

Indexed as

Antineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCell Line, TumorCisplatinDNA DamageDrug Resistance, NeoplasmFlow CytometryFluorescent Antibody TechniqueGene Knockdown TechniquesHumansLung NeoplasmsMultienzyme ComplexesReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSulfate AdenylyltransferaseAntineoplastic AgentsCisplatinMultienzyme ComplexesPAPS synthetaseRNA, Small InterferingSulfate AdenylyltransferaseDNA damagenon-small cell lung cancerPAPSS1sensitizationsiRNA screen

Identifiers

PMID26220590
PMCPMC4627299
OpenAlexW1554155783

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.