Evidence map›Paper›PMID 30894018›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019

PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia.

Fabrizio Pin, Leah J Novinger, Joshua R Huot, Robert A Harris, Marion E Couch, Thomas M O'Connell, Andrea Bonetto

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  9. Article
  10. Article
  11. Article
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  13. Article
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  15. Article
  16. Article
  17. Diversity in chemotherapy-induced cachexia.American journal of physiology. Cell physiology · 2025
    Review
  18. Article
  19. Review
  20. 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 1 country.

Fabrizio PinDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Leah J NovingerDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Joshua R HuotIndiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Robert A HarrisDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Marion E CouchIndiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Thomas M O'ConnellIndiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Andrea BonettoDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Indiana University School of MedicineIndiana University – Purdue University Indianapolis · USUniversity of Indianapolis · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Jun Wan · 1999 to 2026
$59.3M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
NCATS NIH HHS UL1 TR001108NCI NIH HHS P30 CA082709
6 · The paper itself

Abstract

Cachexia is frequently accompanied by severe metabolic derangements, although the mechanisms responsible for this debilitating condition remain unclear. Pyruvate dehydrogenase kinase (PDK)4, a critical regulator of cellular energetic metabolism, was found elevated in experimental models of cancer, starvation, diabetes, and sepsis. Here we aimed to investigate the link between PDK4 and the changes in muscle size in cancer cachexia. High PDK4 and abnormal energetic metabolism were found in the skeletal muscle of colon-26 tumor hosts, as well as in mice fed a diet enriched in Pirinixic acid, previously shown to increase PDK4 levels. Viral-mediated PDK4 overexpression in myotube cultures was sufficient to promote myofiber shrinkage, consistent with enhanced protein catabolism and mitochondrial abnormalities. On the contrary, blockade of PDK4 was sufficient to restore myotube size in C2C12 cultures exposed to tumor media. Our data support, for the first time, a direct role for PDK4 in promoting cancer-associated muscle metabolic alterations and skeletal muscle atrophy.-Pin, F., Novinger, L. J., Huot, J. R., Harris, R. A., Couch, M. E., O'Connell, T. M., Bonetto, A. PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia.

Indexed as

AnimalsCachexiaCell LineMaleMiceMitochondria, MuscleMuscle, SkeletalMuscular AtrophyNeoplasmsOxidation-ReductionPyruvate Dehydrogenase Acetyl-Transferring KinasePdk4 protein, mousePyruvate Dehydrogenase Acetyl-Transferring KinaseC2C12 myotubeschemotherapyenergy metabolismmitochondriaskeletal muscle atrophy

Identifiers

PMID30894018
PMCPMC6529344
OpenAlexW2925166956

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.