Publications by authors named "Raul Fierro Velasco"
PTEN is a multifaceted tumor suppressor that is highly sensitive to alterations in expression or function. The PTEN C-tail domain, which is rich in phosphorylation sites, has been implicated in PTEN stability, localization, catalytic activity, and protein interactions, but its role in tumorigenesis remains unclear. To address this, we utilized several mouse strains with nonlethal C-tail mutations.
View Article and Find Full Text PDFSuper-enhancers regulate genes with important functions in processes that are cell type-specific or define cell identity. Mouse embryonic fibroblasts establish 40 senescence-associated super-enhancers regardless of how they become senescent, with 50 activated genes located in the vicinity of these enhancers. Here we show, through gene knockdown and analysis of three core biological properties of senescent cells that a relatively large number of senescence-associated super-enhancer-regulated genes promote survival of senescent mouse embryonic fibroblasts.
View Article and Find Full Text PDFFoxM1 activates genes that regulate S-G2-M cell-cycle progression and, when overexpressed, is associated with poor clinical outcome in multiple cancers. Here we identify FoxM1 as a tumor suppressor in mice that, through its N-terminal domain, binds to and inhibits Ect2 to limit the activity of RhoA GTPase and its effector mDia1, a catalyst of cortical actin nucleation. FoxM1 insufficiency impedes centrosome movement through excessive cortical actin polymerization, thereby causing the formation of non-perpendicular mitotic spindles that missegregate chromosomes and drive tumorigenesis in mice.
View Article and Find Full Text PDFArticle Synopsis
- Senescent cells (SNCs) weaken the fibrous cap that protects against plaque rupture in arteries, which can lead to heart attacks and strokes.
- By using pharmacological methods or genetic alterations to eliminate SNCs in mice with atherosclerosis, researchers found that cap integrity improved, as shown by increased vascular smooth muscle cell (VSMC) numbers and thickness of the cap.
- The study reveals that SNCs hinder VSMC behavior crucial for cap reinforcement by interfering with insulin-like growth factor-1 (IGF-1), suggesting that targeted therapies combining senolytics or IGFBP-3 inhibition with lipid-lowering medications might be effective against atherosclerosis.
Background & Aims: The CCNE1 locus, which encodes cyclin E1, is amplified in many types of cancer cells and is activated in hepatocellular carcinomas (HCCs) from patients infected with hepatitis B virus or adeno-associated virus type 2, due to integration of the virus nearby. We investigated cell-cycle and oncogenic effects of cyclin E1 overexpression in tissues of mice.
Methods: We generated mice with doxycycline-inducible expression of Ccne1 (Ccne1 mice) and activated overexpression of cyclin E1 from age 3 weeks onward.