Evidence mapPaperPMID 35563313Full record

ArticleInternational journal of molecular sciences2022

CD44+ and CD133+ Non-Small Cell Lung Cancer Cells Exhibit DNA Damage Response Pathways and Dormant Polyploid Giant Cancer Cell Enrichment Relating to Their p53 Status.

Margarita Pustovalova, Taisia Blokhina, Lina Alhaddad, Anna Chigasova, Roman Chuprov-Netochin, Alexander Veviorskiy, Gleb Filkov, Andreyan N Osipov, Sergey Leonov

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

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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.

Margarita PustovalovaSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Taisia BlokhinaSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Lina AlhaddadSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Anna ChigasovaSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Roman Chuprov-NetochinSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Alexander VeviorskiyN.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia.
Gleb FilkovSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Andreyan N OsipovSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.ORCID 0000-0001-5921-9056
Sergey LeonovSchool of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.ORCID 0000-0002-3425-723X
Moscow Institute of Physics and Technology · RUSemenov Institute of Chemical Physics · RU

Funding

Ministry of Science and Higher Education of the Russian Federation 075-15-2020-917Russian Science Foundation 19-74-10096
6 · The paper itself

Abstract

Cancer stem cells (CSCs) play a critical role in the initiation, progression and therapy relapse of many cancers including non-small cell lung cancer (NSCLC). Here, we aimed to address the question of whether the FACS-sorted CSC-like (CD44 + &CD133 +) vs. non-CSC (CD44-/CD133- isogenic subpopulations of p53wt A549 and p53null H1299 cells differ in terms of DNA-damage signaling and the appearance of "dormant" features, including polyploidy, which are early markers (predictors) of their sensitivity to genotoxic stress. X-ray irradiation (IR) at 5 Gy provoked significantly higher levels of the ATR-Chk1/Chk2-pathway activity in CD44-/CD133- and CD133+ subpopulations of H1299 cells compared to the respective subpopulations of A549 cells, which only excited ATR-Chk2 activation as demonstrated by the Multiplex DNA-Damage/Genotoxicity profiling. The CD44+ subpopulations did not demonstrate IR-induced activation of ATR, while significantly augmenting only Chk2 and Chk1/2 in the A549- and H1299-derived cells, respectively. Compared to the A549 cells, all the subpopulations of H1299 cells established an increased IR-induced expression of the γH2AX DNA-repair protein. The CD44-/CD133- and CD133+ subpopulations of the A549 cells revealed IR-induced activation of ATR-p53-p21 cell dormancy signaling-mediated pathway, while none of the CD44+ subpopulations of either cell line possessed any signs of such activity. Our data indicated, for the first time, the transcription factor MITF-FAM3C axis operative in p53-deficient H1299 cells, specifically their CD44+ and CD133+ populations, in response to IR, which warrants further investigation. The p21-mediated quiescence is likely the predominant surviving pathway in CD44-/CD133- and CD133+ populations of A549 cells as indicated by single-cell high-content imaging and analysis of Ki67- and EdU-coupled fluorescence after IR stress. SA-beta-galhistology revealed that cellular-stress-induced premature senescence (SIPS) likely has a significant influence on the temporary dormant state of H1299 cells. For the first time, we demonstrated polyploid giant and/or multinucleated cancer-cell (PGCC/MGCC) fractions mainly featuring the progressively augmenting Ki67

Indexed as

Carcinoma, Non-Small-Cell LungDNA DamageLung NeoplasmsAC133 AntigenCell Line, TumorCytokinesDNAGiant CellsHumansHyaluronan ReceptorsKi-67 AntigenNeoplasm ProteinsNeoplastic Stem CellsPolyploidySignal TransductionTumor Suppressor Protein p53AC133 AntigenCD44 protein, humanCytokinesDNAFAM3C protein, humanHyaluronan ReceptorsKi-67 AntigenNeoplasm ProteinsTumor Suppressor Protein p53cancer stem cellsFAM3CMITFnon-small cell lung cancerp21p53polyploid giant cancer cellsradioresistancesenescence-associated β-galactosidaseγH2AX

Identifiers

PMID35563313
PMCPMC9101266
OpenAlexW4225143067

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.