A5003734971- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Ultrasound and Hyperthermia Applications
- Molecular Biology Techniques and Applications
- Digestive system and related health
- Kruppel-like factors research
- Gastrointestinal Bleeding Diagnosis and Treatment
- RNA modifications and cancer
- biodegradable polymer synthesis and properties
- DNA Repair Mechanisms
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Ultrasound Imaging and Elastography
- Cell Adhesion Molecules Research
- Gastric Cancer Management and Outcomes
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Galectins and Cancer Biology
- Epigenetics and DNA Methylation
- Ultrasound and Cavitation Phenomena
- 3D Printing in Biomedical Research
University of Dundee
2013-2023
Cancer Research UK
2004
Cardiff University
2004
Inserm
2004
Stanford University
1990-1997
University of California, San Francisco
1989-1993
Although Apc is well characterized as a tumor-suppressor gene in the intestine, precise mechanism of this suppression remains to be defined. Using novel inducible Ahcre transgenic line conjunction with loxP-flanked allele we, show that loss acutely activates Wnt signaling through nuclear accumulation β-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such Apc-deficient cells maintain “crypt progenitor-like” phenotype. Critically, for first time...
Calcium-dependent cell-cell adhesion is mediated by the cadherin family of cell proteins. Transduction into cellular reorganization regulated cytosolic proteins, termed alpha-, beta-, and gamma-catenin (plakoglobin), that bind to cytoplasmic domain cadherins link them cytoskeleton. Previous studies cadherin/catenin complex assembly organization relied on coimmunoprecipitation with antibodies, were limited analysis Triton X-100 (TX-100)-soluble fraction these These concluded only one exists...
Mutations in the adenomatous polyposis coli (APC) gene are linked to polyp formation familial and sporadic colon cancer, but functions of protein not known. We show that APC localizes mainly clusters puncta near ends microtubules extend into actively migrating regions epithelial cell membranes. This subcellular distribution requires microtubules, actin filaments. protein-containing membranes involved migration response wounding monolayers, addition motorgen hepatocyte growth factor, during...
The cadherin/catenin complex plays important roles in cell adhesion, signal transduction, as well the initiation and maintenance of structural functional organization cells tissues. In preceding study, we showed that assembly is temporally regulated, novel combinations catenin cadherin complexes are formed both Triton X-100-soluble -insoluble fractions; proposed a model which pools catenins regulating E-cadherin/catenin complexes. Here, sought to determine spatial distributions E-cadherin,...
The Axin‐dependent phosphorylation of β‐catenin catalysed by glycogen synthase kinase‐3 (GSK3) is inhibited during embryogenesis. This protects against ubiquitin‐dependent proteolysis, leading to its accumulation in the nucleus, where it controls expression genes important for development. Frequently rearranged advanced T‐cell lymphomas 1 (FRAT1) a mammalian homologue GSK3‐binding protein (GBP), which appears play key role correct establishment dorsal‐ventral axis Xenopus laevis . Here, we...
Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition chromosomal instability is an early event these tumors. We provide evidence that loss APC leads to partial interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show inhibition U2OS cells compromises spindle checkpoint. This accompanied by decrease association checkpoint proteins Bub1 BubR1 with kinetochores. Additionally, depletion...
The crypts of the intestinal epithelium house stem cells that ensure continual renewal epithelial line tract. Crypt number increases by a process called crypt fission, division single into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. mechanisms governing are poorly understood. However, only knowing how operates can cancer-associated changes be...
Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development colon cancers in familial and sporadic cases. In addition to its role regulating β-catenin levels Wnt signaling pathway, APC is implicated cytoskeletal organization. stabilizes microtubules vivo vitro, this may play a cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, S. Tsukita. 2000. 148:505–517; Zumbrunn,...
Most sporadic colorectal tumors carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein is involved many processes that govern gut tissue. In addition to its involvement regulation of beta-catenin, a cytoskeletal regulator with direct and indirect effects on microtubules. Cancer-related lack binding sites for microtubules APC, suggesting loss this function contributes defects APC-mutant cells. study, we show results disappearance cellular protrusions...
In interphase cells, the adenomatous polyposis coli (APC) protein accumulates on a small subset of microtubules (MTs) in cell protrusions, suggesting that APC may regulate dynamics these MTs. We comicroinjected nonperturbing fluorescently labeled monoclonal antibody and tubulin to simultaneously visualize endogenous MTs living cells. decorated with spent more time growing had decreased catastrophe frequency compared non-APC-decorated Endogenous associated briefly shortening To determine...
The role of the 100-kDa polypeptide components clathrin-coated vesicles in endocytosis was investigated by microinjection specific monoclonal antibodies. Receptor-mediated uptake transferrin and liposomes quantitatively inhibited. These results show that polypeptides are directly involved localized clathrin assembly at cell periphery markers for endocytic pathway. This demonstrates an situ function these protein complexes which they found.
Contributions of null and hypomorphic alleles Apc in mice produce both developmental pathophysiological phenotypes. To ascribe the resulting genotype-to-phenotype relationship unambiguously to Wnt/β-catenin pathway, we challenged allele combinations by genetically restricting intracellular β-catenin expression corresponding compound mutant mice. Subsequent evaluation extent Tcf4-reporter activity mouse embryo fibroblasts enabled genetic measurement signaling form an allelic series mutants....
Despite high rates of cell death, epithelia maintain intact barriers by squeezing dying cells out using a process termed extrusion. Cells can extrude apically into the lumen or basally tissue epithelium encases, depending on whether actin and myosin contract at base apex, respectively. We previously found that microtubules in surrounding target p115 RhoGEF to cortex control where contraction occurs. However, what controls microtubule targeting also extrusion direction were unclear. Here we...