14 research outputs found
Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes
Src-transformed cells hijack mitosis to extrude from the epithelium
Potentially cancerous cells undergo live apical extrusion from normal monolayers and vSrc expression induces this in zebrafish epithelia. Here, the authors show that vSrc coordinates cytokinetic ring formation, cell cycle progression, junctional integrity, cell survival and apicobasal polarity to induce extrusion of transformed cells
Calcium Wave Promotes Cell Extrusion
When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis. However, the underlying molecular mechanism still remains elusive. In this study, we first show, using mammalian cultured epithelial cells and zebrafish embryos, that prior to apical extrusion of RasV12-transformed cells, calcium wave occurs from the transformed cell and propagates across the surrounding cells. The calcium wave then triggers and facilitates the process of extrusion. IP3 receptor, gap junction, and mechanosensitive calcium channel TRPC1 are involved in calcium wave. Calcium wave induces the polarized movement of the surrounding cells toward the extruding transformed cells. Furthermore, calcium wave facilitates apical extrusion, at least partly, by inducing actin rearrangement in the surrounding cells. Moreover, comparable calcium propagation also promotes apical extrusion of apoptotic cells. Thus, calcium wave is an evolutionarily conserved, general regulatory mechanism of cell extrusion
Inhibition of carbonyl reductase activity in pig heart by alkyl phenyl ketones
The inhibitory effects of alkyl phenyl ketones on carbonyl reductase activity were examined in pig heart. In this study, carbonyl reductase activity was estimated as the ability to reduce 4-benzoylpyridine to S(-)-α-phenyl-4-pyridylmethanol in the cytosolic fraction from pig heart (pig heart cytosol). The order of their inhibitory potencies for the enzyme activity was hexanophenone > valerophenone > heptanophenone > butyrophenone > propiophenone. The inhibitory potencies of acetophenone and nonanophenone were much lower. A significant relationship was observed between Vmax/Km values for the reduction of alkyl phenyl ketones and their inhibitory potencies for carbonyl reductase activity in pig heart cytosol. Furthermore, hexanophenone was a competitive inhibitor for the enzyme activity. These results indicate that several alkyl phenyl ketones including hexanophenone inhibit carbonyl reductase activity in pig heart cytosol, by acting as substrate inhibitors