El miércoles 27 de septiembre del 2017 organizamos en la Fundación Ramón Areces un Simposio Internacional sobre nuevas perspectivas en la investigación sobre el cáncer. En colaboración con el Centro Nacional de Investigaciones Oncológicas (CNIO) y Weizmann Institute for Science.
13. Abnormal structure of arterias in Plk1(+/-) mice
AS
DIA
SR
Structural alterations in the arterial elastic layer & lost of elasticity
Increase internal diameter in arteries & aneurisms
15. (Plk1_lox)
X
(SM22a-CreERT2)
Specific ablation of Plk1 in Smooth Muscle Cells
Plk1 (lox/lox) (D/D)SM
lox
D
M - H A H A
- TMX + TMX
(H) - heart (A) - aorta
Specific ablation in
arterias
Hypotension
16. Specific ablation of Plk1 in Smooth Muscle Cells
10 weeks old
Angiotensin II
Deficient contraction Protected from
hypertension
17. Lack of contraction of actomyosin fibers
Smooth muscle cells isolated from mutant mice
Actomyosin contraction is a RhoA-dependent process
24. A conserved mechanism in Plk1 function
Plk1 RhoA
Cytokinesis Blood pressure
PLk1
Contraction
25. A syndrome with Plk1 haploinsufficiency
Ballif et al. (2007) Nat. Genet. 39:107
PLK1
Skull phenotype
− Head circumference
− Flat face
− Frontal bossing
− Short nose with wide nasal bridge
Psychomotor and Cognitive delay
Cardiovasular disease
26. Take-Home messages
Plk1 is a major regulator of RhoA activity during acto-myosin
contraction:
a conserved function from yeast to mammals
a conserved function from proliferating to differentiated
cells
not only in cytokinesis: also during contraction of arterias
Mouse models provide a unique system to understand the
physiological relevance of proteins; hopefully before their inhibitors
reach the Clinic
Arteria function and structure should be monitored during therapeutic
treatments with volasertib against cancer (e.g. AML)
27. Mónica Alvarez-
Fernández
Guillermo de Cárcer
Aisha El-Bakali
José González-Martínez
Begoña Hurtado
Carolina Maestre
María Maroto
Diego Martínez-Alonso
Anna F. B. Martins
Marianna Trakala
María Salazar-Roa
Belén Sanz
María Sanz Flores
Elisabet Zapatero
X. Bustelo, M.A. Sevilla, M.J. Montero (CIC, Univ. Salamanca)
S. Martínez-Martínez, J. Oller, N. Méndez-Barbero, J.M. Redondo (CNIC)
Cell Division and Cancer Group
Spanish National Cancer Research Centre (CNIO)