Evidence map›Paper›PMID 34330897›Full record

ArticleNature communications2021

AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing.

Georgios I Laliotis, Evangelia Chavdoula, Maria D Paraskevopoulou, Abdul Kaba, Alessandro La Ferlita, Satishkumar Singh, Vollter Anastas, Keith A Nair, Arturo Orlacchio, Vasiliki Taraslia and 10 more

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 3 countries.

Georgios I LaliotisDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA. glaliot1@jhmi.edu.ORCID http://orcid.org/0000-0001-9205-8258
Evangelia ChavdoulaDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Maria D ParaskevopoulouMolecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA.
Abdul KabaDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Alessandro La FerlitaDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Satishkumar SinghThe Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.
Vollter AnastasDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-5078-2838
Keith A NairDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-6777-456X
Arturo OrlacchioDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Vasiliki TarasliaMolecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA.
Ioannis VlachosDIANA-Lab, Hellenic Pasteur Institute, Athens, Greece.
Marina CapeceDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Artemis HatzigeorgiouDIANA-Lab, Hellenic Pasteur Institute, Athens, Greece.
Dario PalmieriDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
Christos TsatsanisSchool of Medicine, University of Crete, Heraklion, Crete, Greece.
Salvatore AlaimoDepartment of Clinical and Experimental Medicine, Bioinformatics Unit, University of Catania, Catania, Italy.ORCID http://orcid.org/0000-0003-4825-7617
Lalit SehgalThe Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.ORCID http://orcid.org/0000-0002-1151-5427
David P CarboneThe Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.ORCID http://orcid.org/0000-0003-3002-1921
Vincenzo CoppolaDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-6163-1779
Philip N TsichlisDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA. Philip.tsichlis@osumc.edu.ORCID http://orcid.org/0000-0002-5300-0448
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USTufts Medical Center · USTufts University · USUniversity of Crete · GRBeth Israel Deaconess Medical Center · USPasteur Hellenic Institute · GRUniversity of Catania · IT

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
The role of IWS1 in development and tumorigenesisR01CA198117 · NCI · TUFTS MEDICAL CENTER · PI COPPOLA, VINCENZO, TSICHLIS, PHILIP N. · 2015 to 2019
$2.9M
Differential Regulation of RNA processing by Akt isoformsR01CA186729 · NCI · TUFTS MEDICAL CENTER · PI TSICHLIS, PHILIP N. · 2015 to 2019
$1.8M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA186729NCI NIH HHS R01 CA198117
6 · The paper itself

Abstract

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficient U2AF2 splice variant. Here, we show that exon 2 inclusion in the U2AF2 mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes. The exon 2-deficient U2AF2 mRNA encodes a Serine-Arginine-Rich (RS) domain-deficient U2AF65, which is defective in CDCA5 pre-mRNA processing. This results in downregulation of the CDCA5-encoded protein Sororin, a phosphorylation target and regulator of ERK, G2/M arrest and impaired cell proliferation and tumor growth. Analysis of human lung adenocarcinomas, confirmed activation of the pathway in EGFR-mutant tumors and showed that pathway activity correlates with tumor stage, histologic grade, metastasis, relapse after treatment, and poor prognosis.

Indexed as

A549 CellsAdenocarcinoma of LungAnimalsCell CycleCell Line, TumorCell ProliferationErbB ReceptorsGene Expression ProfilingGene Expression Regulation, NeoplasticHEK293 CellsHumansKaplan-Meier EstimateLung NeoplasmsMiceMice, Inbred NODMice, KnockoutErbB ReceptorsIws1 protein, humanProto-Oncogene Proteins c-aktRNA-Binding ProteinsSplicing Factor U2AFTranscription FactorsU2AF2 protein, human

Identifiers

PMID34330897
PMCPMC8324843
OpenAlexW3185225358

What OpenQuestion 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 OpenQuestion graph.