Evidence map›Paper›PMID 40314847›Full record

ArticleAngiogenesis2025

Mixed lineage kinase (MLK) controls tumor development and angiogenesis.

Shashi Kant, Amada D Caliz, Hyung-Jin Yoo, Gaganpreet Kaur, Heather Learnard, Hassan A Khalil, Roger J Davis, John F Jr Keaney

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angiogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

8 authors.

Shashi KantDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. skant1@bwh.harvard.edu.
Amada D CalizDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Hyung-Jin YooDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Gaganpreet KaurDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Heather LearnardDivision of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Hassan A KhalilDivision of Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Roger J DavisProgram of Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
John F Jr KeaneyDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Funding

Mixed Lineage Kinase 2 (MLK2) in tumor angiogenesisR03CA295675 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$83k
American Heart Association 25POST1373333NCATS NIH HHS R03 TR004452NCI NIH HHS R03 CA295675NHLBI NIH HHS R01 HL151626
6 · The paper itself

Abstract

Cancer is among the leading causes of death in the USA and worldwide. Solid tumors require the formation of new blood vessels (angiogenesis) for their growth. The endothelium plays a crucial role in angiogenesis and tumor progression. Hypoxic stress generated by tumors can activate stress kinases such as mixed lineage kinases (MLKs). Publicly available datasets on lung adenocarcinoma, along with our experimental findings, indicate that MLK2 and MLK3 are expressed in human lung tumors. In this study, using three distinct mouse models of tumor development, we demonstrated that MLK2 (MAP3K10) and MLK3 (MAP3K11) are essential for tumor growth and angiogenesis. Furthermore, MLK2 and MLK3 are highly expressed in the endothelium and are necessary for endothelial proliferation, migration, and angiogenesis. In the endothelium, MLKs regulate the expression of angiogenic growth factors and metalloproteinases, including Pgf, Vegfa, Angptl4, Adam8, and Mmp9. Additionally, the MLK family of kinases acts through the long noncoding RNA (lncRNA) H19 to control the expression of these pro-angiogenic factors in the endothelium. Collectively, these findings suggest that the MLK-H19 axis coordinates endothelial function, angiogenesis, and tumor growth.

Indexed as

Lung NeoplasmsMAP Kinase Kinase KinasesNeovascularization, PathologicAngiogenesisAnimalsCell ProliferationGene Expression Regulation, NeoplasticHumansMiceMitogen-Activated Protein Kinase Kinase Kinase 11RNA, Long NoncodingMAP Kinase Kinase KinasesMitogen-Activated Protein Kinase Kinase Kinase 11RNA, Long NoncodingAngiogenesisCancerGrowth factorHypoxiaNoncoding RNASignaling

Identifiers

PMID40314847
PMCPMC12697148

What Socratic holds

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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 Socratic graph.