![]() ![]() Finally, steady progress has been made in trapping and cooling neutral atoms. Positrons have been accumulated in large numbers in similar traps, and low-energy positron or positronium beams have been generated. In recent years, impressive progress has been achieved at the Low-Energy Antiproton Ring (LEAR) at CERN in capturing antiprotons in specially designed Penning traps, in cooling them to energies of a few milli-electron volts, and storing them for hours in a small volume of space. Equally important is the question of the gravitational acceleration of antimatter. The study of CPT invariance with the highest achievable precision in all particle sectors is of fundamental importance for physics. In this large collection of copy number profiles, deletions on chromosome 4q35 containing FAT1 were frequent (834 tumors 26.6%) and were observed in 8 of 14 cancer types, including central nervous system, colorectal, ovarian To identify candidate tumor suppressor genes on chromosome 4q35, we began by examining this region using an array compara tive genomic hybridization (aCGH) data set from 3,131 cancer samples (Tumorscape data set) 39. RESULTS Deletion at 4q35 in multiple cancer types The broad nature of copynumber loss on chromosome 4q35 has made identification of the driving gene(s) in this region difficult. Here, we present genetic, functional and mechanistic data that identify the protocadherin FAT1 gene at 4q35 as a tumor suppressor that, when inactivated, leads to aberrant Wnt/βcatenin signaling in multiple types of cancer. If not sequestered at the cell membrane, βcatenin binds to the Tcell factor (TCF) proteins, which translocate to the nucleus and activate Wnt target genes 22,37, promoting cell proliferation, tumor growth and stem cell identity 22,24,36,38. Cadherinrelated pro teins can interact with βcatenin and sequester it at the cell periphery, thereby regulating its transcriptional activity 32–36. However, the genetic basis of Wnt pathway activation in other cancer types is not well understood. In certain cancers, including colorectal carcinoma, this activation is frequently due to alteration of Wnt pathway genes, commonly APC or CTNNB1 mutation 27–31. Aberrant activation of the Wnt/βcatenin pathway drives the development of many types of human malignancy 22–26. Although FAT1 has been shown to regulate cellcell association and actin dynamics 10, the role of this protein in cancer was unknown. In human cells, FAT1 protein is localized to the cell membrane, often concentrated at filo podia, lamellipodia and sites of cellcell contact. In contrast, FAT1 is not thought to have a strong role in these processes 9,18–21. fat has the greatest homo logy with mammalian FAT4, which has been implicated in both planar cell polarity and Hippo signaling 13–17. In Drosophila, loss of fat leads to cell cycle dysregulation and hyper proliferation in larval imaginal discs 9–12. In mammals, the FAT family includes FAT1, FAT2, FAT3 and FAT4, all related to the Drosophila tumor suppressor fat, which is known to have an important role in key developmental processes 7–9. The functions of protocadherin proteins remain incompletely understood. FAT1 encodes a member of the FAT protocadherin family, a group of transmembrane proteins com monly expressed in epithelial tissues. We have identified frequent somatic mutations in the FAT1 gene, located at 4q35.2. Type) tests of decoherence-induced CPT violation, which may characterise someĪ r t i c l e s Chromosome 4q35 is frequently lost in numerous types of human cancer, and it has been hypothesized that this region contains a tumor suppressor gene 1–6. Providing independent tests of CPT symmetry, as well as novel ("smoking-gun" Providing independent measurements of T(ime reversal) and CP Violation, thus I also mention the r\^ole of entangled states of neutral mesons in Then Iĭescribe briefly some tests of these symmetries, giving emphasis in low-energyĪntiproton physics and electric dipole moment measurements, of interest to thisĬonference. In this way I estimate some of theĬoefficients of the Standard Model Extension (SME), which is a framework for aįield theoretic study of such a breakdown of fundamental symmetries. Of matter over antimatter in the Universe. Gravity setting, nevertheless there are situations in which these violationsĪre due to a given classical background geometry that may characterised earlyĮpochs of our Universe, and in fact be responsible for the observed dominance Although the latter symmetries may be violated in a quantum I review first some theoretical motivations for violation of Lorentz and/orĬPT Invariance. ![]()
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