Evidence map›Paper›PMID 27050456›Full record

ArticleAutophagy2016

Inhibition of BMI1 induces autophagy-mediated necroptosis.

Anindya Dey, Soumyajit Banerjee Mustafi, Sounik Saha, Shailendra Kumar Dhar Dwivedi, Priyabrata Mukherjee, Resham Bhattacharya

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
5.7field-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

49 citing papers in PubMed, 111 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

6 authors at 2 institutions in 1 country.

Anindya Deya Department of Obstetrics and Gynecology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
Soumyajit Banerjee Mustafia Department of Obstetrics and Gynecology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
Sounik Sahab Department of Pathology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
Shailendra Kumar Dhar Dwivedia Department of Obstetrics and Gynecology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
Priyabrata Mukherjeeb Department of Pathology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
Resham Bhattacharyaa Department of Obstetrics and Gynecology , Stephenson Cancer Center, University of Oklahoma Health Science Center , Oklahoma City , OK , USA.
University of Oklahoma Health Sciences Center · USUniversity of Oklahoma · US

Funding

Bmi-1, a potential therapeutic target in ovarian cancerR01CA157481 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BHATTACHARYA, RESHAM · 2012 to 2016
$1.6M
NCI NIH HHS CA157481NCI NIH HHS R01 CA157481
6 · The paper itself

Abstract

The clonal self-renewal property conferred by BMI1 is instrumental in maintenance of not only normal stem cells but also cancer-initiating cells from several different malignancies that represent a major challenge to chemotherapy. Realizing the immense pathological significance, PTC-209, a small molecule inhibitor of BMI1 transcription has recently been described. While targeting BMI1 in various systems significantly decreases clonal growth, the mechanisms differ, are context-dependent, and somewhat unclear. We report here that genetic or pharmacological inhibition of BMI1 significantly impacts clonal growth without altering CDKN2A/INK4/ARF or CCNG2 and induces autophagy in ovarian cancer (OvCa) cells through ATP depletion. While autophagy can promote survival or induce cell death, targeting BMI1 engages the PINK1-PARK2-dependent mitochondrial pathway and induces a novel mode of nonapoptotic, necroptosis-mediated cell death. In OvCa, necroptosis is potentiated by activation of the RIPK1-RIPK3 complex that phosphorylates its downstream substrate, MLKL. Importantly, genetic or pharmacological inhibitors of autophagy or RIPK3 rescue clonal growth in BMI1 depleted cells. Thus, we have established a novel molecular link between BMI1, clonal growth, autophagy and necroptosis. In chemoresistant OvCa where apoptotic pathways are frequently impaired, necroptotic cell death modalities provide an important alternate strategy that leverage overexpression of BMI1.

Indexed as

ApoptosisAutophagyAdenosine TriphosphateCaspasesCell Line, TumorHeterocyclic Compounds, 2-RingHumansMitochondriaModels, BiologicalNecrosisPolycomb Repressive Complex 1ThiazolesAdenosine TriphosphateBMI1 protein, humanCaspasesHeterocyclic Compounds, 2-RingPolycomb Repressive Complex 1PTC-209ThiazolesautophagyBMI1necroptosisovarian cancerPTC-209

Identifiers

PMID27050456
PMCPMC4836029
OpenAlexW2313960655

What OpenQuestion holds

Textmetadata
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.