RT Journal Article
T1 High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition
A1 Sartages García, Miriam
A1 Floridia, Ebel
A1 García Colomer, Mar
A1 Iglesias García, Cristina
A1 Macía Cortiñas, Manuel
A1 Peñas Silva, Patricia
A1 Couraud, Pierre-Olivier
A1 Romero, Ignacio A.
A1 Weksler, Babette
A1 Pombo Ramos, Celia María
A1 Zalvide Torrente, Juan Bautista
K1 Cavernoma
K1 CCM3
K1 PDCD10
K1 EGFR
K1 VEGFR2
K1 ErbB2
K1 Lapatinib
AB Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells. By comparing protein expression in control and CCM3-silenced cells, we found that the levels of the Epidermal Growth Factor Receptor (EGFR) are higher in CCM3-deficient cells, which adds to the known upregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in these cells. Whereas VEGFR2 is upregulated at the mRNA level, EGFR has a prolonged half-life. Inhibition of EGFR family members in CCM3-deficient cells does not revert the known cellular effects of lack of CCM genes, but it induces significantly more apoptosis in CCM3-deficient cells than in control cells. We propose that the susceptibility to tyrosine kinase inhibitors of CCM3-deficient cells can be harnessed to kill the abnormal cells of these lesions and thus treat CCMs pharmacologically
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/24201
UL http://hdl.handle.net/10347/24201
LA eng
NO Sartages, M.; Floridia, E.; García-Colomer, M.; Iglesias, C.; Macía, M.; Peñas, P.; Couraud, P.-O.; Romero, I.A.; Weksler, B.; Pombo, C.M.; Zalvide, J. High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition. Biomedicines 2020, 8, 624
NO This work was supported by grants to C.M.P. and J.Z. from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación of Spain (SAF2017-87691-R), the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (ED431C 2019/13). Support from Centro singular de investigación de Galicia, accreditation 2016–2019, ED431G/05)and the European Regional Development Fund (ERDF), is gratefully acknowledged. M.S. is a predoctoral fellow from Xunta de Galicia
DS Minerva
RD 22 abr 2026