A Common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice.

Background: Genome-wide association studies have identified an exon 6 deletion variant proposed to increase pancreatic cancer risk.

Objective: To acquire evidence on its causal role, we developed and analysed a new mouse strain carrying an equivalent variant in , the mouse orthologue.

Design: We used CRISPR/Cas9 to introduce a 707 bp deletion encompassing exon 6 ( ).

A common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice.

Objective: Genome wide association studies have identified an exon 6 deletion variant that associates with increased risk of pancreatic cancer. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in , the mouse orthologue of .

Design: We used CRISPR/Cas9 to introduce a 707bp deletion in encompassing exon 6 ( ).

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects.

c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial.

Introduction: Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 (ClinicalTrials.

Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non-small Cell Lung Cancer.

Purpose: Hypoxia is associated with poor prognosis and is predictive of poor response to cancer treatments, including radiotherapy. Developing noninvasive biomarkers that both detect hypoxia prior to treatment and track change in tumor hypoxia following treatment is required urgently.

Experimental Design: We evaluated the ability of oxygen-enhanced MRI (OE-MRI) to map and quantify therapy-induced changes in tumor hypoxia by measuring oxygen-refractory signals in perfused tissue (perfused Oxy-R).

Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer.

The exact identity of castrate-resistant (CR) cells and their relation to CR prostate cancer (CRPC) is unresolved. We use single-cell gene profiling to analyze the molecular heterogeneity in basal and luminal compartments. Within the luminal compartment, we identify a subset of cells intrinsically resistant to castration with a bi-lineage gene expression pattern.

From meiosis to mitosis - the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus.

Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle.

Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly.

The essential mammalian gene TACC3 is frequently mutated and amplified in cancers and its fusion products exhibit oncogenic activity in glioblastomas. TACC3 functions in mitotic spindle assembly and chromosome segregation. In particular, phosphorylation on S558 by the mitotic kinase, Aurora-A, promotes spindle recruitment of TACC3 and triggers the formation of a complex with ch-TOG-clathrin that crosslinks and stabilises kinetochore microtubules.

Centrosomes and mitotic spindle poles: a recent liaison?

Centrosomes comprise two cylindrical centrioles embedded in the pericentriolar material (PCM). The PCM is an ordered assembly of large scaffolding molecules, providing an interaction platform for proteins involved in signalling, trafficking and most importantly microtubule nucleation and organization. In mitotic cells, centrosomes are located at the spindle poles, sites where spindle microtubules converge.

XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation.

chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly.

Dissecting the role of Aurora A during spindle assembly.

The centrosomal kinase Aurora A (AurA) is required for cell cycle progression, centrosome maturation and spindle assembly. However, the way it participates in spindle assembly is still quite unclear. Using the Xenopus egg extract system, we have dissected the role of AurA in the different microtubule (MT) assembly pathways involved in spindle formation.

The TACC proteins: TACC-ling microtubule dynamics and centrosome function.

A major quest in cell biology is to understand the molecular mechanisms underlying the high plasticity of the microtubule network at different stages of the cell cycle, and during and after differentiation. Initial reports described the centrosomal localization of proteins possessing transforming acidic coiled-coil (TACC) domains. This discovery prompted several groups to examine the role of TACC proteins during cell division, leading to indications that they are important players in this complex process in different organisms.

Spindle-localized CPE-mediated translation controls meiotic chromosome segregation.

Meiotic progression requires the translational activation of stored maternal mRNAs, such as those encoding cyclin B1 or mos. The translation of these mRNAs is regulated by the cytoplasmic polyadenylation element (CPE) present in their 3'UTRs, which recruits the CPE-binding protein CPEB. This RNA-binding protein not only dictates the timing and extent of translational activation by cytoplasmic polyadenylation but also participates, together with the translational repressor Maskin, in the transport and localization, in a quiescent state, of its targets to subcellular locations where their translation will take place.

Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis.

The Xenopus protein Maskin has been previously identified and characterized in the context of its role in translational control during oocyte maturation. Maskin belongs to the TACC protein family. In other systems, members of this family have been shown to localize to centrosomes during mitosis and play a role in microtubule stabilization.