Evidence map›Paper›PMID 42582009›Full record

ArticlebioRxiv : the preprint server for biology2026

Lysyl oxidase drives ccRCC progression by coordinating HIF-2α transcription program with tumor microenvironment.

Burge Ulukan, Ozge Saatci, Ariel Madrigal, Minjun Kim, Wensheng Tian, Mustafa Soytas, Zohreh Mehrjoo, Ozlem Sener Sahin, Kukkamadi Sreenivas, Chintada Nageswara Rao and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Burge UlukanDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.ORCID 0000-0002-1101-8834
Ozge SaatciDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.
Ariel MadrigalDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0G1, Canada.
Minjun KimDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0G1, Canada.
Wensheng TianDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Mustafa SoytasVictor P. Dahdaleh Institute of Genomic Medicine, Montreal, QC, H3A 0G1, Canada.
Zohreh MehrjooDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0G1, Canada.
Ozlem Sener SahinDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.
Kukkamadi SreenivasDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA.
Chintada Nageswara RaoDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA.
Tamiko NishimuraVictor P. Dahdaleh Institute of Genomic Medicine, Montreal, QC, H3A 0G1, Canada.
Virginie PillonRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3A 1A3, Canada.
Jean-Sebastian AnomaDepartment of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA.
Elizabeth HillDepartment of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA.
Janusz RakResearch Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Campbell McInnesDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA.
Morag ParkRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3A 1A3, Canada.
Fadi BrimoDepartment of Oncology, McGill University, Montreal, QC, H3A 0G4, Canada.
Simon TanguayDivision of Urology and Uro-oncology, McGill University. Montreal, QC, H4A 0B1, Canada.
Ryan Charles RussellDepartment of Pathology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
Hamed NajafabadiDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0G1, Canada.ORCID 0000-0003-2735-4231
Yasser RiazalhosseiniDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0G1, Canada.
Ozgur SahinDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI John J Lemasters · 2009 to 2026
$42.7M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI CROUCH, ROSALIE K · 2002 to 2002
$2.0M
Overcoming chemoresistance in triple negative breast cancerR01CA267101 · NCI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI Ozgur Sahin · 2022 to 2026
$1.8M
Inhibiting tumor growth and metastasis in highly aggressive breast cancers with centrosome amplificationR01CA251374 · NCI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI SAHIN, OZGUR · 2021 to 2025
$1.7M
Confocal/Multiphoton Microscope UpgradeS10OD018113 · OD · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI LEMASTERS, JOHN J · 2015 to 2015
$570k
NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA251374NCI NIH HHS R01 CA267101NCRR NIH HHS C06 RR015455NIH HHS S10 OD018113
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is driven by persistent HIF-2α transcription program initiated by VHL loss, yet molecular mediators sustaining this program are poorly defined. Using single-cell transcriptomics, we identified lysyl oxidase (LOX) as a driver of ccRCC progression, selectively enriched in a hypoxia/epithelial-mesenchymal transition (EMT) gene program associated with poor outcome. While LOX oxidizes and stabilizes HIF-2α by antagonizing HUWE1-mediated ubiquitination and degradation, thereby sustaining HIF-2α-driven transcription in cancer cells, it also remodels extracellular matrix (ECM) and promotes angiogenesis in the tumor microenvironment (TME). Genetic or pharmacological inhibition of LOX destabilizes HIF-2α, disrupts ECM, inhibits angiogenesis, and suppresses tumor initiation, growth, and metastasis in vivo. LOX inhibition enhances anti-angiogenic therapy response and remains effective in belzutifan-resistant HIF-2α G323E-mutant tumors. Nuclear LOX protein correlates with nuclear HIF-2α in high-grade patient tumors. Together, LOX coordinates HIF-2α transcription program with TME and is a therapeutic target in ccRCC.

Indexed as

angiogenesisclear cell renal cell carcinomaHIF-2α proteostasislysyl oxidasepseudohypoxiasingle-cell transcriptomicstherapeutic resistancetumor microenvironment

Identifiers

PMID42582009
PMCPMC13456076

What OpenQuestion 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 OpenQuestion graph.