@misc{10481/95423,
year = {2023},
month = {2},
url = {https://hdl.handle.net/10481/95423},
abstract = {Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of
endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a
previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression
(CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic
approach, we have found that β-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant
melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VEcadherin
upon FAK disabling resulted in VE-Cadherin/β-catenin complex dissociation, increased β-catenin degradation while
reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses
β-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits
stabilization of β-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK
inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single
treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous
origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the
cooperation of β-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.},
organization = {Spanish Ministry of Economy and
Competitiveness SAF2015-70520-R},
organization = {Spanish Ministry of Science and Technology RTI2018-098968-B-I00, CIBERONC ISCIII CB16/12/00421},
organization = {Junta de Andalucía, a
project of Excellence from Junta de Andalucía P10-CTS-0662, P12-CTS-383},
organization = {Fundación Domingo Martínez to FJO. Consejería de Economía, Innovación, Ciencia y
Empleo, Junta de Andalucía (PAIDI 2020, POSTDOC_21_00865) to DD-B. Fundación
Getthi ONC18PE01/2022 to DAE, AT},
publisher = {Springer Nature},
title = {VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry},
doi = {10.1038/s41419-023-05666-7},
author = {Delgado Bellido, Daniel and Zamudio Martínez, Esteban and Fernández Cortés, Mónica and Herrera-Campos, Ana Belén and Olmedo-Pelayo, Joaquin and Jordán Perez, Carmen and Expósito Hernández, José and de Álava, Enrique and Amaral, Ana Teresa and O´Valle, Francisco and Díaz García, José Ángel and Oliver, F. Javier},
}