Evidence map›Paper›PMID 28032863›Full record

ArticleCell death & disease2016

Short-term inhibition of TERT induces telomere length-independent cell cycle arrest and apoptotic response in EBV-immortalized and transformed B cells.

Andrea Celeghin, Silvia Giunco, Riccardo Freguja, Manuela Zangrossi, Silvia Nalio, Riccardo Dolcetti, Anita De Rossi

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

30 citing papers in PubMed, 51 citations in OpenAlex.

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  18. Cancer-specific loss ofProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Frontiers in oncology · 2021
    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

7 authors at 3 institutions in 2 countries.

Andrea CeleghinSection of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Silvia GiuncoSection of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Riccardo FregujaSection of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Manuela ZangrossiSection of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Silvia NalioImmunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV)-IRCCS, Padova, Italy.
Riccardo DolcettiCancer Bio-Immunotherapy Unit, CRO-IRCCS, National Cancer Institute, Aviano, Italy.
Anita De RossiSection of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.ORCID 0000-0001-6435-7509
University of Padua · ITIstituto Oncologico Veneto · ITTranslational Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Besides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumorigenesis through extra-telomeric functions. The possible therapeutic effects of BIBR1532 (BIBR), a powerful TERT inhibitor, have been evaluated in different cellular backgrounds, but no data are currently available regarding Epstein-Barr virus (EBV)-driven B-cell malignancies. Our aim was to characterize the biological effects of TERT inhibition by BIBR on EBV-immortalized lymphoblastoid cell lines (LCLs) and fully transformed Burkitt's lymphoma (BL) cell lines. We found that BIBR selectively inhibits telomerase activity in TERT-positive 4134/Late and 4134/TERT+ LCLs and EBV-negative BL41 and EBV-positive BL41/B95.8 BL cell lines. TERT inhibition led to decreased cell proliferation, accumulation of cells in the S-phase and ultimately to increased apoptosis, compared with mock-treated control cells. All these effects occurred within 72 h and were not observed in BIBR-treated TERT-negative 4134/TERT- and U2OS cells. The cell cycle arrest and apoptosis, consequent upon short-term TERT inhibition, were associated with and likely dependent on the activation of the DNA damage response (DDR), highlighted by the increased levels of γH2AX and activation of ATM and ATR pathways. Analyses of the mean and range of telomere lengths and telomere dysfunction-induced foci indicated that DDR after short-term TERT inhibition was not related to telomere dysfunction, thus suggesting that TERT, besides stabilizing telomere, may protect DNA via telomere-independent mechanisms. Notably, TERT-positive LCLs treated with BIBR in combination with fludarabine or cyclophosphamide showed a significant increase in the number of apoptotic cells with respect to those treated with chemotherapeutic agents alone. In conclusion, TERT inhibition impairs cell cycle progression and enhances the pro-apoptotic effects of chemotherapeutic agents in TERT-positive cells. These results support new therapeutic applications of TERT inhibitors in EBV-driven B-cell malignancies.

Indexed as

Telomere HomeostasisAminobenzoatesApoptosisAtaxia Telangiectasia Mutated ProteinsB-LymphocytesCell Cycle CheckpointsCell Line, TransformedCell SurvivalCyclophosphamideHerpesvirus 4, HumanHistonesHumansNaphthalenesSignal TransductionS PhaseTelomeraseAminobenzoatesAtaxia Telangiectasia Mutated ProteinsATR protein, humanBIBR 1532CyclophosphamidefludarabineH2AX protein, humanHistonesNaphthalenesTelomeraseTERT protein, humanVidarabine

Identifiers

PMID28032863
PMCPMC5260987
OpenAlexW2562983694

What OpenQuestion holds

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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.