Evidence map›Paper›PMID 34183356›Full record

ArticleCancer research2021

Stress-Mediated Reprogramming of Prostate Cancer One-Carbon Cycle Drives Disease Progression.

Nora Pällmann, Ke Deng, Marte Livgård, Martina Tesikova, Yixin Jin, Nicolai Sebastian Frengen, Nermin Kahraman, Hamada M Mokhlis, Bulent Ozpolat, Wanja Kildal and 8 more

Open access · bronzeAbstract read
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In one paragraph

Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 5 countries.

Nora Pällmann *Department of Biosciences, University of Oslo, Oslo, Norway.
Ke Deng *Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Marte LivgårdDepartment of Biosciences, University of Oslo, Oslo, Norway.
Martina TesikovaDepartment of Mathematics and Science, University of South-Eastern Norway, Borre, Norway.
Yixin JinDepartment of Biosciences, University of Oslo, Oslo, Norway.
Nicolai Sebastian FrengenDepartment of Biosciences, University of Oslo, Oslo, Norway.ORCID 0000-0003-1834-7638
Nermin KahramanGynecological Oncology, MD Anderson Cancer Center, Houston, Texas.
Hamada M MokhlisGynecological Oncology, MD Anderson Cancer Center, Houston, Texas.
Bulent OzpolatGynecological Oncology, MD Anderson Cancer Center, Houston, Texas.
Wanja KildalInstitute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-9639-6868
Havard Emil DanielsenInstitute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Ladan FazliThe Vancouver Prostate Centre, Vancouver, BC, Canada.
Paul S RennieThe Vancouver Prostate Centre, Vancouver, BC, Canada.
Partha P BanerjeeDepartment of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia.
Aykut ÜrenLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.ORCID 0000-0002-2033-1216
Yang JinDepartment of Biosciences, University of Oslo, Oslo, Norway.
Omer F KuzuDepartment of Biosciences, University of Oslo, Oslo, Norway. fahris@ibv.uio.no o.f.kuzu@ibv.uio.no.
Fahri SaatciogluDepartment of Biosciences, University of Oslo, Oslo, Norway. fahris@ibv.uio.no o.f.kuzu@ibv.uio.no.
Oslo University Hospital · NOUniversity of Oslo · NOThe University of Texas MD Anderson Cancer Center · USGeorgetown University · USPrevention of Organ Failure · CAUniversity of South-Eastern Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

One-carbon (1C) metabolism has a key role in metabolic programming with both mitochondrial (m1C) and cytoplasmic (c1C) components. Here we show that activating transcription factor 4 (ATF4) exclusively activates gene expression involved in m1C, but not the c1C cycle in prostate cancer cells. This includes activation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression, the central player in the m1C cycle. Consistent with the key role of m1C cycle in prostate cancer, MTHFD2 knockdown inhibited prostate cancer cell growth, prostatosphere formation, and growth of patient-derived xenograft organoids. In addition, therapeutic silencing of MTHFD2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in preclinical prostate cancer mouse models. Consistently, MTHFD2 expression is significantly increased in human prostate cancer, and a gene expression signature based on the m1C cycle has significant prognostic value. Furthermore, MTHFD2 expression is coordinately regulated by ATF4 and the oncoprotein c-MYC, which has been implicated in prostate cancer. These data suggest that the m1C cycle is essential for prostate cancer progression and may serve as a novel biomarker and therapeutic target. SIGNIFICANCE: These findings demonstrate that the mitochondrial, but not cytoplasmic, one-carbon cycle has a key role in prostate cancer cell growth and survival and may serve as a biomarker and/or therapeutic target.

Indexed as

AnimalsCarbon CycleCell Line, TumorCell ProliferationDisease ProgressionHumansMaleMiceMice, NudeProstatic Neoplasms

Identifiers

PMID34183356
OpenAlexW3176982346

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.