Cited by 185Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerPancreatic and Hepatic Oncology Research

Targeting Mitochondrial Complex I Overcomes Chemoresistance in High OXPHOS Pancreatic Cancer

Open access
Masoud, Rawand, Reyes-Castellanos, Gabriela, Lac, Sophie, Garcia, Julie, Dou, Samir, Shintu, Laetitia, Abdel Hadi, Nadine, Gicquel, Tristan +10 more·2020·Cell Reports Medicine

Abstract

Mitochondrial respiration (oxidative phosphorylation, OXPHOS) is an emerging target in currently refractory cancers such as pancreatic ductal adenocarcinoma (PDAC). However, the variability of energetic metabolic adaptations between PDAC patients has not been assessed in functional investigations. In this work, we demonstrate that OXPHOS rates are highly heterogeneous between patient tumors, and that high OXPHOS tumors are enriched in mitochondrial respiratory complex I at protein and mRNA levels. Therefore, we treated PDAC cells with phenformin (complex I inhibitor) in combination with standard chemotherapy (gemcitabine), showing that this treatment is synergistic specifically in high OXPHOS cells. Furthermore, phenformin cooperates with gemcitabine in high OXPHOS tumors in two orthotopic mouse models (xenografts and syngeneic allografts). In conclusion, this work proposes a strategy to identify PDAC patients likely to respond to the targeting of mitochondrial energetic metabolism in combination with chemotherapy, and that phenformin should be clinically tested in appropriate PDAC patient subpopulations.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.xcrm.2020.100143

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The regulatory consequences of Sp/Klf motif enrichment are in genes associated with modulation of reactive oxygen species and metabolism such as SOD1, ID1, and NDUFV2.

    “In doing so, we find that the regulatory consequences of Sp/Klf motif enrichment are in genes associated with modulation of reactive oxygen species and metabolism such as SOD144, ID145, and NDUFV246.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Masoud, R., Reyes-Castellanos, G., Lac, S., Garcia, J., Dou, S., Shintu, L., Abdel Hadi, N., Gicquel, T., El Kaoutari, A., Diémé, B., Tranchida, F., Cormareche, L., Borge, L., Gayet, O., Pasquier, E., Dusetti, N., Iovanna, J., & Carrier, A.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Masoud, Rawand
  • Carrier, Alice
Venue
Cell Reports Medicine
Publisher
Elsevier BV
Published
2020-11
Volume
1
Issue
8
Pages
100143
ISSN
2666-3791 (ISSN-L)
OpenAlex
W3101012847
Cited by
175
References
47
Citations by year
2026: 14 · 2025: 35 · 2024: 49 · 2023: 27 · 2022: 27 · 2021: 23
FWCI
6.93
Type
journal article
Language
en
Open access
Locations
  • Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL AMU (submittedVersion, cc-by-nc-nd)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • Institut National Du Cancer
  • Fondation ARC pour la Recherche sur le Cancer (PJA 20151203544)
  • La Ligue Nationale contre le Cancer
  • DGOS
  • Fondation Amidex
  • Fondation de France
  • Canceropôle Provence-Alpes-Côte d’Azur
  • Fédération GEFLUC
  • Fondation pour la Recherche Médicale
  • CONACYT (339091/471717)
  • IMODI
  • Association Azm et Saadé
  • Agence Nationale de la Recherche
  • Canceropôle PACA
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
pancreatic ductal adenocarcinoma, mitochondrial complex I, oxidative phosphorylation, chemoresistance, phenformin, gemcitabine, combination chemotherapy, tumor metabolic heterogeneity, mitochondrial respiration, synergistic drug combination, patient stratification
MeSH terms
PC-3 Cells, Gemcitabine, Animals, Deoxycytidine, Female, Humans, Male, Mice, Inbred C57BL, Mice, Nude, Mitochondria, Oxidative Phosphorylation, Pancreatic Neoplasms, Phenformin, Drug Resistance, Neoplasm, Cell Respiration, Carcinoma, Pancreatic Ductal, Xenograft Model Antitumor Assays, Electron Transport Complex I, Cell Line, Tumor, Cell Proliferation, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review