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ZEB1 and Uveal Melanoma Invasiveness. / Zhilnikova, Maria; Balantaeva, Maria; Zvereva, Sofia et al.

In: International Journal of Molecular Sciences, Vol. 26, No. 21, 10346, 24.10.2025.

Research output: Contribution to journal › Article › peer-review

Harvard

Zhilnikova, M, Balantaeva, M, Zvereva, S, Biryukov, M, Atamanov, V, Poletaeva, J, Ryabchikova, E, Stanishevskaya, O, Chernykh, D, Kononova, N & Koval, O 2025, 'ZEB1 and Uveal Melanoma Invasiveness', International Journal of Molecular Sciences, vol. 26, no. 21, 10346. https://doi.org/10.3390/ijms262110346

APA

Zhilnikova, M., Balantaeva, M., Zvereva, S., Biryukov, M., Atamanov, V., Poletaeva, J., Ryabchikova, E., Stanishevskaya, O., Chernykh, D., Kononova, N., & Koval, O. (2025). ZEB1 and Uveal Melanoma Invasiveness. International Journal of Molecular Sciences, 26(21), [10346]. https://doi.org/10.3390/ijms262110346

Vancouver

Zhilnikova M, Balantaeva M, Zvereva S, Biryukov M, Atamanov V, Poletaeva J et al. ZEB1 and Uveal Melanoma Invasiveness. International Journal of Molecular Sciences. 2025 Oct 24;26(21):10346. doi: 10.3390/ijms262110346

Author

Zhilnikova, Maria ; Balantaeva, Maria ; Zvereva, Sofia et al. / ZEB1 and Uveal Melanoma Invasiveness. In: International Journal of Molecular Sciences. 2025 ; Vol. 26, No. 21.

BibTeX

@article{aaee51ff6bf2484a98134d9ac64ee6f7,
title = "ZEB1 and Uveal Melanoma Invasiveness",
abstract = "Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adults. Transcription factor ZEB1 is one of the potential master regulators of melanocytes plasticity, because it is recognized as a {"}driver{"} of epithelial-to-mesenchymal transitions (EMTs) in carcinomas. We studied the correlation of tumor invasiveness with ZEB1 status and vascular endothelial growth factor/its receptor (VEGF-A/VEGFR2) in UM cells, and also with melanocyte's differentiation rate. Eight UM cell cultures were characterized by melanosomes content using an ETM. ZEB1, VEGF-A and VEGFR2 levels in UM cells were detected by RT-PCR, Western blot, ELISA and flow cytometry. Effects of siRNA-dependent ZEB1 knockdown on UM cell proliferation and their sensitivity to the VEGF-A inhibitor Eylea (aflibercept) were tested by MTT and in a real-time proliferation assay. UMs with an invasive growth type can maintain a high degree of melanocyte differentiation. All ZEB1low cells were obtained from spindle cell tumors. The sensitivity of UM cells to Eylea inversely correlated with the level of the VEGFR2 receptor. ZEB1 knockdown completely blocked VEGF-A production while anti-VEGF treatment stimulated ZEB1 increase. In UM cell cultures, ZEB1 is a positive regulator of VEGF-A expression. In addition, there is probably a ZEB1 feedback loop that is sensitive to a drop in VEGF-A concentration. The data obtained allow us to consider ZEB1 silencing as an auxiliary link for a combined strategy of killing UM cells.",
keywords = "Humans, Zinc Finger E-box-Binding Homeobox 1/metabolism, Melanoma/pathology, Uveal Neoplasms/pathology, Uveal Melanoma, Vascular Endothelial Growth Factor A/metabolism, Cell Line, Tumor, Cell Proliferation, Vascular Endothelial Growth Factor Receptor-2/metabolism, Neoplasm Invasiveness, Gene Expression Regulation, Neoplastic, Melanocytes/metabolism, Cell Differentiation, Epithelial-Mesenchymal Transition",
author = "Maria Zhilnikova and Maria Balantaeva and Sofia Zvereva and Mikhail Biryukov and Vasiliy Atamanov and Julia Poletaeva and Elena Ryabchikova and Olga Stanishevskaya and Dmitryi Chernykh and Natalia Kononova and Olga Koval",
note = "The study was supported by the grant of the Russian Science Foundation № 23-14-00285.",
year = "2025",
month = oct,
day = "24",
doi = "10.3390/ijms262110346",
language = "English",
volume = "26",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "21",

}

RIS

TY - JOUR

T1 - ZEB1 and Uveal Melanoma Invasiveness

AU - Zhilnikova, Maria

AU - Balantaeva, Maria

AU - Zvereva, Sofia

AU - Biryukov, Mikhail

AU - Atamanov, Vasiliy

AU - Poletaeva, Julia

AU - Ryabchikova, Elena

AU - Stanishevskaya, Olga

AU - Chernykh, Dmitryi

AU - Kononova, Natalia

AU - Koval, Olga

N1 - The study was supported by the grant of the Russian Science Foundation № 23-14-00285.

PY - 2025/10/24

Y1 - 2025/10/24

N2 - Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adults. Transcription factor ZEB1 is one of the potential master regulators of melanocytes plasticity, because it is recognized as a "driver" of epithelial-to-mesenchymal transitions (EMTs) in carcinomas. We studied the correlation of tumor invasiveness with ZEB1 status and vascular endothelial growth factor/its receptor (VEGF-A/VEGFR2) in UM cells, and also with melanocyte's differentiation rate. Eight UM cell cultures were characterized by melanosomes content using an ETM. ZEB1, VEGF-A and VEGFR2 levels in UM cells were detected by RT-PCR, Western blot, ELISA and flow cytometry. Effects of siRNA-dependent ZEB1 knockdown on UM cell proliferation and their sensitivity to the VEGF-A inhibitor Eylea (aflibercept) were tested by MTT and in a real-time proliferation assay. UMs with an invasive growth type can maintain a high degree of melanocyte differentiation. All ZEB1low cells were obtained from spindle cell tumors. The sensitivity of UM cells to Eylea inversely correlated with the level of the VEGFR2 receptor. ZEB1 knockdown completely blocked VEGF-A production while anti-VEGF treatment stimulated ZEB1 increase. In UM cell cultures, ZEB1 is a positive regulator of VEGF-A expression. In addition, there is probably a ZEB1 feedback loop that is sensitive to a drop in VEGF-A concentration. The data obtained allow us to consider ZEB1 silencing as an auxiliary link for a combined strategy of killing UM cells.

AB - Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adults. Transcription factor ZEB1 is one of the potential master regulators of melanocytes plasticity, because it is recognized as a "driver" of epithelial-to-mesenchymal transitions (EMTs) in carcinomas. We studied the correlation of tumor invasiveness with ZEB1 status and vascular endothelial growth factor/its receptor (VEGF-A/VEGFR2) in UM cells, and also with melanocyte's differentiation rate. Eight UM cell cultures were characterized by melanosomes content using an ETM. ZEB1, VEGF-A and VEGFR2 levels in UM cells were detected by RT-PCR, Western blot, ELISA and flow cytometry. Effects of siRNA-dependent ZEB1 knockdown on UM cell proliferation and their sensitivity to the VEGF-A inhibitor Eylea (aflibercept) were tested by MTT and in a real-time proliferation assay. UMs with an invasive growth type can maintain a high degree of melanocyte differentiation. All ZEB1low cells were obtained from spindle cell tumors. The sensitivity of UM cells to Eylea inversely correlated with the level of the VEGFR2 receptor. ZEB1 knockdown completely blocked VEGF-A production while anti-VEGF treatment stimulated ZEB1 increase. In UM cell cultures, ZEB1 is a positive regulator of VEGF-A expression. In addition, there is probably a ZEB1 feedback loop that is sensitive to a drop in VEGF-A concentration. The data obtained allow us to consider ZEB1 silencing as an auxiliary link for a combined strategy of killing UM cells.

KW - Humans

KW - Zinc Finger E-box-Binding Homeobox 1/metabolism

KW - Melanoma/pathology

KW - Uveal Neoplasms/pathology

KW - Uveal Melanoma

KW - Vascular Endothelial Growth Factor A/metabolism

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Vascular Endothelial Growth Factor Receptor-2/metabolism

KW - Neoplasm Invasiveness

KW - Gene Expression Regulation, Neoplastic

KW - Melanocytes/metabolism

KW - Cell Differentiation

KW - Epithelial-Mesenchymal Transition

U2 - 10.3390/ijms262110346

DO - 10.3390/ijms262110346

M3 - Article

C2 - 41226394

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 21

M1 - 10346

ER -

ID: 72240467