Evidence map›Paper›PMID 39653752›Full record

ArticleNature biotechnology2025

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Esha Madan, António M Palma, Vignesh Vudatha, Amit Kumar, Praveen Bhoopathi, Jochen Wilhelm, Tytus Bernas, Patrick C Martin, Gaurav Bilolikar, Aenya Gogna and 100 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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  7. The human Flower isoform hFWE4 facilitates cornification in cutaneous squamous cell carcinoma.JID innovations : skin science from molecules to population health · 2026
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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

110 authors.

Esha Madan *Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. esha.gogna@vcuhealth.org.ORCID http://orcid.org/0000-0002-4941-0612
António M Palma *Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Vignesh Vudatha *Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Amit Kumar *Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Praveen Bhoopathi *Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Jochen Wilhelm *Institute for Lung Health (ILH), Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Giessen, Germany.ORCID http://orcid.org/0000-0001-5544-9647
Tytus BernasDepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
Patrick C MartinDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4093-8277
Gaurav BilolikarMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Aenya GognaCollegiate School, Richmond, VA, USA.
Maria Leonor PeixotoInstitute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Isabelle DreierUniversities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.ORCID http://orcid.org/0009-0004-0545-3479
Thais Fenz AraujoSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Elena GarreSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Anna GustafssonSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-1107-5361
Kalpana Deepa Priya DorayappanDivision of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Narsimha MamidiWisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0001-8842-4649
Zhaoyu SunEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Michail YekelchykUniversities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Davide AccardiChampalimaud Center for the Unknown, Lisbon, Portugal.ORCID http://orcid.org/0000-0002-2158-8048
Amalie Lykke OlsenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0009-0001-8437-7707
Lin LinDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-7546-4948
Asaf Ashkenazy TitelmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Michael BianchiEmpire Genomics Corp., Depew, NY, USA.
Phil JessmonEmpire Genomics Corp., Depew, NY, USA.
Elnaz Abbasi FaridIndiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN, USA.
Anjan K PradhanDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Lena NeufeldDepartment of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID http://orcid.org/0000-0002-8229-9856
Eilam YeiniDepartment of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Santanu MajiVCU Institute of Molecular Medicine, Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Christopher J PelhamEurofins Panlabs, Inc., St. Charles, MO, USA.
Hyobin KimDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4856-7415
Daniel OhDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hans Olav RolfsnesMolecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.
Rita C MarquesChampalimaud Center for the Unknown, Lisbon, Portugal.
Amy LuMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Masaki NaganeDepartment of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, Japan.
Sahil ChaudharyDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Kartik GuptaDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Keshav C GognaDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Ana BigioChampalimaud Center for the Unknown, Lisbon, Portugal.
Karthikeya BhoopathiMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Padmanabhan MannangattiMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
K Gopinath AcharyIMGENEX India Pvt. Ltd., Bhubaneswar, India.
Javed AkhtarIMGENEX India Pvt. Ltd., Bhubaneswar, India.
Sara BeliãoChampalimaud Center for the Unknown, Lisbon, Portugal.
Swadesh DasMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Isabel CorreiaCentro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.ORCID http://orcid.org/0000-0001-7096-4284
Cláudia L da SilvaInstitute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.ORCID http://orcid.org/0000-0002-1091-7651
Arsénio M FialhoInstitute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Michael J PoellmannPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
Kaila Javius-JonesPharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, USA.
Adam M HawkridgeMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Sanya PalInnomics Inc., Cambridge, MA, USA.
Kumari S ShreeMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Emad A RakhaDepartment of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK.ORCID http://orcid.org/0000-0002-5009-5525
Sambhav KhuranaMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Gaoping XiaoSyd Labs, Inc., Hopkinton, MA, USA.
Dongyu ZhangDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Arjun RijalMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Charles LyonsMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Steven R GrossmanDepartment of Internal Medicine, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0003-4692-6925
David P TurnerDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Raghavendra PillappaDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Karanvir PrakashDepartment of Orthopedic Surgery, Virginia Commonwealth University, Richmond, VA, USA.
Gaurav GuptaVCU Division of Nephrology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
Gary L W G RobinsonPhaseDesign Research, Framingham, MA, USA.ORCID http://orcid.org/0009-0008-1645-5399
Jennifer KoblinskiMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Hongjun WangDepartment of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ, USA.
Gita SinghAbeomics, Inc., San Diego, CA, USA.
Sujay SinghAbeomics, Inc., San Diego, CA, USA.
Sagar RayamajhiDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0001-5420-7873
Manny D BacolodDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-2085-4877
Hope RichardsDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, USA.ORCID http://orcid.org/0000-0002-5956-0585
Sadia SayeedDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
Katherine P KleinDepartment of Obstetrics and Gynecology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
David ChelmowDepartment of Obstetrics and Gynecology, Virginia Commonwealth University, VCU School of Medicine, Richmond, VA, USA.
Ronit Satchi-FainaroDepartment of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID http://orcid.org/0000-0002-7360-7837
Karuppaiyah SelvendiranDivision of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Denise ConnollyFox Chase Cancer Center Biosample Repository Facility, Philadelphia, PA, USA.
Frits Alan ThorsenMolecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.ORCID http://orcid.org/0000-0002-7762-3703
Rolf BjerkvigMolecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway.
Kenneth P NephewIndiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN, USA.ORCID http://orcid.org/0000-0003-2192-1346
Michael O IdowuDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
Mark P KühnelInstitute of Pathology, RWTH Aachen University, Aachen, Germany.
Christopher MoskalukDepartment of Pathology, University of Virginia, Charlottesville, VA, USA.
Seungpyo HongWisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0001-9870-031X
William L RedmondEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Göran LandbergSahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Antonio Lopez-BeltranChampalimaud Center for the Unknown, Lisbon, Portugal.
Andrew S PoklepovicMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Arun SanyalDivision of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Paul B FisherMassey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6232-9969
Usha MenonMRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.ORCID http://orcid.org/0000-0003-3708-1732
Ronny DrapkinPenn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew K GodwinDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0002-3987-9580
Yonglun LuoDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-0007-7759
Maximilian AckermannInstitute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Alexandar TzankovInstitute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1100-3819
Kirsten D MertzInstitute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3074-6925
Danny JonigkInstitute of Pathology, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0002-5251-2281
Allan TsungDepartment of Surgery, Division of Surgical Oncology, University of Virginia, Charlottesville, VA, USA.
David SidranskyDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4178-2072
Jose TrevinoDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Arturo P SaavedraDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Robert WinnDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Kyoung Jae WonDepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
Eduardo MorenoChampalimaud Center for the Unknown, Lisbon, Portugal.ORCID http://orcid.org/0000-0001-5040-452X
Rajan GognaDepartment of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. rajan.gogna@vcuhealth.org.ORCID http://orcid.org/0009-0000-0214-6853

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Transgenic & Gene-Targeting Shared ResourceP30CA168524 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ROY A. JENSEN · 2012 to 2026
$40.1M
Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Diane E Mahoney · 2019 to 2026
$21.5M
Extracellular Vesicle Proteomic Fingerprinting of Ovarian Cancer for Early Detection with a Nanoengineered MicrosystemR01CA260132 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI GODWIN, ANDREW K., ZENG, YONG · 2021 to 2025
$3.4M
Interplay between tumor and microenvironment in bone metastasisR01CA259599 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, WANG, XIANG-YANG SHAWN · 2021 to 2025
$2.3M
NCI NIH HHS P30 CA006927NCI NIH HHS P30 CA016059NCI NIH HHS P30 CA168524NCI NIH HHS R01 CA259599NCI NIH HHS R01 CA260132NIGMS NIH HHS P20 GM130423
6 · The paper itself

Abstract

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

Indexed as

Cell CompetitionOvarian NeoplasmsTumor MicroenvironmentAnimalsCell Line, TumorExosomesFemaleGene Expression Regulation, NeoplasticHumansMiceRNA, Long NoncodingRNA, Long Noncoding

Identifiers

PMID39653752
PMCPMC13595346

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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.