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Advanced prostate cancer preferential metastasis to bone is associated with osteomimicry. MINDIN is a secreted matrix protein upregulated in prostate tumors that overexpresses bone-related genes during prostate cancer progression. Na+/H+ exchanger regulatory factor (NHERF-1) is a scaffold protein that has been involved both in tumor regulation and osteogenesis. We hypothesize that NHERF-1 modulation is a mechanism used by MINDIN to promote prostate cancer progression. We analyzed the expression of NHERF-1 and MINDIN in human prostate samples and in a premetastatic prostate cancer mouse model, based on the implantation of prostate adenocarcinoma TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) cells in immunocompetent C57BL/6 mice. The relationship between NHERF-1 and MINDIN and their effects on cell proliferation, migration, survival and osteomimicry were evaluated. Upregulation of MINDIN and downregulation of NHERF-1 expression were observed both in human prostate cancer samples and in the TRAMP-C1 model. MINDIN silencing restored NHERF-1 expression to control levels in the mouse model. Stimulation with MINDIN reduced NHERF-1 expression and triggered its mobilization from the plasma membrane to the cytoplasm in TRAMP-C1 cells. MINDIN-dependent downregulation of NHERF-1 promoted tumor cell migration and proliferation without affecting osteomimicry and adhesion. We propose that MINDIN downregulates NHERF-1 expression leading to promotion of processes involved in prostate cancer progression. Full article

This essay starts in medias res, in the puzzling reappearance of the classical metaphor of Bildung as the transformation of man’s “first” animal nature into the “second” cultivated one. I call it the two-natures metaphor. I think it misrepresents children by prescribing form rather than asking what actually takes form in the child’s mind—in his/her relationship with adults. It made me wonder whether this mistake also lingers on in the current discourse on education. I then turn to aspects of John Dewey’s subtle and revolutionary critique of the classical theory of formation, but also to make the controversial point that he, too, seems to miss the importance of the child’s internal point of view. The importance of the subjective life of the child is suggested first by reinscribing Rousseau and Kant into the intersubjective theories of Hegel and Dewey; second, by reference to recent studies in developmental psychology that offer detailed and in-depth descriptions of our relationship with children. My basic point of departure is the existential encounters between children and adults, for example, as part of classroom practices. The title has a double connotation. It means that theory must be taken as the measure of practice. It means, too, that practice must work as the measure of theory. I will, in the main, try and pursue the last course. Full article