Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox‐1 homeobox transcription factor
Open accessAbstract
Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of approximately 40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.
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PROX1 can function as a master regulator of lymphatic endothelial cells.
“Notably, PROX1 can function as an activator to promote neurogenesis in the brain39,40, or as a master regulator of lymphatic endothelial cells41,42.”
From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [41]
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- Authors
- Petrova, T. V., Mäkinen, T., Mäkelä, T. P., Saarela, J., Virtanen, I., Ferrell, R. E., Finegold, D. N., Kerjaschki, D., Ylä‐Herttuala, S., & Alitalo, K.
- Affiliations
- University of Helsinki (FI)
- Ludwig Cancer Research (BE)
- University of Pittsburgh (US)
- University of Vienna (AT)
- University of Eastern Finland (FI)
- Corresponding author
- Alitalo, Kari
- ORCID
- Venue
- The EMBO Journal
- Published
- 2002-09-02
- Volume
- 21
- Issue
- 17
- Pages
- 4593-4599
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC125413
- OpenAlex
- W2092619818
- Cited by
- 632
- References
- 1
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 11 · 2023: 10 · 2022: 19 · 2021: 27 · 2020: 22 · 2019: 16 · 2018: 16 · 2017: 21 · 2016: 19 · 2015: 30 · 2014: 33 · 2013: 32 · 2012: 39
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- Prox1, homeodomain transcription factor, lymphatic endothelial cells, transcriptional reprogramming, cyclin E1, cyclin E2, cell proliferation, lymphatic development, metastasis
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Cell Differentiation, Cell Division, Cells, Cultured, Cytoskeletal Proteins, Endothelium, Lymphatic, Endothelium, Vascular, Gene Expression Regulation, Humans, Organ Specificity, Phenotype, Promoter Regions, Genetic, Recombinant Fusion Proteins, Transcription Factors, Transcription, Genetic, Cell Adhesion Molecules, Cytokines, Cyclins, Mutagenesis, Site-Directed, Extracellular Matrix Proteins, Receptors, Cytokine, Homeodomain Proteins, Dermis, Tumor Suppressor Proteins
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