Evidence map›Paper›PMID 35267651›Full record

ArticleCancers2022

Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells.

Jernej Repas, Mateja Zupin, Maja Vodlan, Peter Veranič, Boris Gole, Uroš Potočnik, Mojca Pavlin

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  19. Metformin and Its Immune-Mediated Effects in Various Diseases.International journal of molecular sciences · 2023
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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

7 authors at 2 institutions in 1 country.

Jernej RepasInstitute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
Mateja ZupinCenter for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, SI-2000 Maribor, Slovenia.
Maja VodlanInstitute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.ORCID 0000-0002-9414-7286
Peter VeraničInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.ORCID 0000-0003-1999-9988
Boris GoleCenter for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, SI-2000 Maribor, Slovenia.ORCID 0000-0002-2461-6729
Uroš PotočnikCenter for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, SI-2000 Maribor, Slovenia.ORCID 0000-0003-1624-9428
Mojca PavlinInstitute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.ORCID 0000-0001-5477-7833
University of Ljubljana · SIUniversity of Maribor · SI

Funding

Slovenian Research Agency P1-0055, J3-6794, J7-7424., P3-0067
6 · The paper itself

Abstract

Metformin and 2-deoxy-D-glucose (2DG) exhibit multiple metabolic and immunomodulatory anti-cancer effects, such as suppressed proliferation or PD-L1 expression. Their combination or 2DG alone induce triple-negative breast cancer (TNBC) cell detachment, but their effects on mitochondria, crucial for anchorage-independent growth and metastasis formation, have not yet been evaluated. In the present study, we explored the effects of metformin, 2DG and their combination (metformin + 2DG) on TNBC cell mitochondria in vitro. Metformin + 2DG increased mitochondrial mass in TNBC cells. This was associated with an increased size but not number of morphologically normal mitochondria and driven by the induction of mitochondrial biogenesis rather than suppressed mitophagy. 2DG and metformin + 2DG strongly induced the unfolded protein response by inhibiting protein N-glycosylation. Together with adequate energy stress, this was one of the possible triggers of mitochondrial enlargement. Suppressed N-glycosylation by 2DG or metformin + 2DG also caused PD-L1 deglycosylation and reduced surface expression in MDA-MB-231 cells. PD-L1 was increased in low glucose and normalized by both drugs. 2DG and metformin + 2DG reduced PD-1 expression in Jurkat cells beyond the effects on activation, while cytokine secretion was mostly preserved. Despite increasing mitochondrial mass in TNBC cells, metformin and 2DG could therefore potentially be used as an adjunct therapy to improve anti-tumor immunity in TNBC.

Indexed as

2-deoxy-D-glucoseAMPKanchorage-independenceER stressmetforminmitochondrial biogenesisPD-1/PD-L1 axisprotein N-glycosylationT cellstriple-negative breast cancer

Identifiers

PMID35267651
PMCPMC8909901
OpenAlexW4220852548

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.