Kyoto University · Biochemistry, Genetics and Molecular Biology
Professor Yasuyuki Fujita's research lab focuses on the cellular and molecular mechanisms underlying epithelial homeostasis and early carcinogenesis, with a central emphasis on cell competition, tumor suppressor functions, and epithelial defense against cancer (EDAC). The lab investigates how normal and transformed epithelial cells interact at the interface, particularly the roles of proteins such as Lgl and mutant p53 in inducing selective elimination of pre-cancerous cells through apoptosis or necroptosis. Using Drosophila and mouse models, along with quantitative proteomics and live imaging, the lab explores how metabolic stress, inflammation, and soluble factors like ADAMDEC1 modulate these competitive interactions. A key theme is understanding how microenvironmental cues and systemic conditions—such as high-fat diet—compromise EDAC and promote tumor initiation.
Figures are computed from collected data and may differ slightly.
During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby "loser cells" undergo apoptosis are not clearly understood. Lgl (lethal
Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelial tissues via cell competition with the surrounding normal epithelial cells. This cancer preventive phenomenon is termed epithelial defense against cancer (EDAC). However, it remains largely unknown whether and how EDAC is diminished during carcinogenesis. In this study, using a cell competition mouse model, we show that high-fat diet (HFD) feeding substantially attenuates the frequency of apica
p53 is a tumor suppressor protein, and its missense mutations are frequently found in human cancers. During the multi-step progression of cancer, p53 mutations generally accumulate at the mid or late stage, but not in the early stage, and the underlying mechanism is still unclear. In this study, using mammalian cell culture and mouse ex vivo systems, we demonstrate that when p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells, mutant p53 cells undergo necroptosis and
Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelia via cell competition with the surrounding normal epithelial cells. However, it remains unknown whether and how soluble factors are involved in this cancer preventive phenomenon. By performing stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative mass spectrometric analyses, we have identified ADAM-like Decysin-1 (ADAMDEC1) as a soluble protein whose expression is u
Cell transformation arises from activation of oncoproteins and ⁄ or inactivation of tumor suppressor proteins. During the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial monolayer. However, it is not known what happens at the interface between normal and transformed cells once the initial transformation has occurred. Using elaborate cell culture systems, recent reports have shown that interactions between normal and transformed epithelial cells can in
In epithelial cells, morphology is intrinsically related to function. Typically, polarization (i.e. acquisition of a cuboidal cell shape) must occur prior to terminal differentiation and functionality of epithelial sheets. Extensive work has been performed to understand the initial steps that drive cell-cell contact assembly, a process that is essential for polarization. However, not much is known about the subsequent steps that lead to remodelling of actin cytoskeleton and concomitant cell shap
Rabphilin-3A is a putative target protein for Rab3A, a small GTP-binding protein particularly implicated in neurotransmitter release. Rabphilin-3A interacts more preferentially with GTP-Rab3A than with GDP-Rab3A. Moreover, Rabphilin-3A shows a weak activity to stimulate the GTPase activity of Rab3A and a strong activity to inhibit the Rab3A GTPase-activating protein (GAP)-stimulated GTPase activity of Rab3A. Here, we show that Rabphilin-3A has another activity to stimulate the GDP/GTP exchange r
Previous studies have revealed that, at the initial step of carcinogenesis, transformed cells are often eliminated from epithelia via cell competition with the surrounding normal cells. In this study, we performed cell competition-based high-throughput screening for chemical compounds using cultured epithelial cells and confocal microscopy. PLX4720 was identified as a hit compound that promoted apical extrusion of RasV12-transformed cells surrounded by normal epithelial cells. Knockdown/knockout
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