Evidence map›Paper›PMID 40339577›Full record

ArticleDevelopmental cell2025

Lymphatic endothelial mTORC1 instructs metabolic and developmental signaling during lymphangiogenesis.

Fei Han, Summer Simeroth, Jie Zhu, Irma Gryniuk, Atul Pranay, Weiqing Chen, Yuan Wang, Yuanyuan Cai, Zhiyuan Shen, Guangyu Wang and 3 more

Abstract read
In one paragraph

Article in Developmental cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
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

13 authors.

Fei HanCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Summer SimerothCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jie ZhuCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Irma GryniukCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Atul PranayAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Weiqing ChenCenter for Bioinformatics and Computational Biology, Houston Methodist Research Institute, Houston, TX, USA; Department of Physiology, Biophysics & Systems Biology, Weill Cornell Graduate School of Medical Science, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Yuan WangDepartment of Radiation Oncology, Rutgers Cancer Institute and Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
Yuanyuan CaiCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Zhiyuan ShenDepartment of Radiation Oncology, Rutgers Cancer Institute and Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
Guangyu WangCenter for Bioinformatics and Computational Biology, Houston Methodist Research Institute, Houston, TX, USA; Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX, USA; Center for RNA Therapeutics, Houston Methodist Research Institute, Houston, TX, USA; Department of Cardiothoracic Surgery, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Courtney T GriffinCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Lijun XiaCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Pengchun YuCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: pengchun-yu@omrf.org.

Funding

Viral sensor IFIH1 promotes SLE through an altered interferon programP20GM139763 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI Kenneth M Humphries · 2021 to 2026
$20.3M
Project 4: The BRCA Network in Medulloblastoma Responses to Replication StressP01CA250957 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI DE, SUBHAJYOTI · 2021 to 2025
$11.3M
Molecular modulators of radiation-induced chromosome instability and hematopoietic damageR01CA195612 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI SHEN, ZHIYUAN · 2015 to 2025
$3.6M
Metabolic mechanisms controlling lymphatic vessel formationR01HL162985 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI PENGCHUN YU · 2022 to 2026
$2.2M
Regulation of Ku70 methylation and functions by SETD4R01CA260724 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI SHEN, ZHIYUAN · 2021 to 2025
$1.8M
Site-1 protease-mediated lipid metabolism in lymphatic vascular developmentR01HL153728 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI XIA, LIJUN · 2020 to 2023
$1.7M
NCI NIH HHS P01 CA250957NCI NIH HHS R01 CA195612NCI NIH HHS R01 CA260724NHLBI NIH HHS R01 HL153728NHLBI NIH HHS R01 HL162985NIGMS NIH HHS P20 GM139763
6 · The paper itself

Abstract

The lymphatic vasculature comprises lymphatic capillaries and collecting vessels. To support lymphatic development, lymphatic endothelial cells (LECs) utilize nutrients to fuel lymphangiogenic processes. Meanwhile, LECs maintain constant prospero homeobox 1 (PROX1) expression critical for lymphatic specification. However, molecular mechanisms orchestrating nutrient metabolism while sustaining PROX1 levels in LECs remain unclear. Here, we show that loss of RAPTOR, an indispensable mechanistic target of rapamycin complex 1 (mTORC1) component, downregulates PROX1 and impairs lymphatic capillary growth and differentiation of collecting lymphatics in mice. Mechanistically, mTORC1 inhibition in mouse and human LECs causes Myc reduction, which decreases hexokinase 2 (HK2) and glutaminase (GLS), inhibiting glycolysis and glutaminolysis. Myc or HK2/GLS ablation impedes lymphatic capillary and collecting vessel formation. Interestingly, mTORC1 regulation of PROX1 is independent of Myc-HK2/GLS signaling. Moreover, genetic interaction analysis indicates that Myc and PROX1 play crucial roles in mTORC1-regulated lymphatic development. Collectively, our findings identify mTORC1 as a key regulator of metabolic programs and PROX1 expression during lymphangiogenesis.

Indexed as

Endothelial CellsLymphangiogenesisLymphatic VesselsMechanistic Target of Rapamycin Complex 1Signal TransductionAnimalsCell DifferentiationHexokinaseHomeodomain ProteinsHumansMiceMice, Inbred C57BLProspero-Related Homeobox 1 ProteinProto-Oncogene Proteins c-mycRegulatory-Associated Protein of mTORTumor Suppressor ProteinsHexokinaseHomeodomain ProteinsMechanistic Target of Rapamycin Complex 1Prospero-Related Homeobox 1 ProteinProto-Oncogene Proteins c-mycRegulatory-Associated Protein of mTORRptor protein, mouseTumor Suppressor Proteinsglutaminaseglutaminolysisglycolysishexokinase 2lymphangiogenesislymphatic endothelial celllymphatic vesselmTORC1MycPROX1

Identifiers

PMID40339577
PMCPMC12353337

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Registered trials

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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.