SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells

AbstractBackgroundSOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression.ResultsHere, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such asAXIN2,DICER1, andDHX9. In addition, SOX4 DNA binding activity to the promoters ofDICER1,AXIN2,DHX9andSOX4itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4-plakoglobin interactions resulted in reduced transcriptional activity of β-catenin luciferase reporters.ConclusionsThese data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression.</jats:sec

SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells

Abstract Background SOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression. Results Here, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such as AXIN2, DICER1, and DHX9. In addition, SOX4 DNA binding activity to the promoters of DICER1, AXIN2, DHX9 and SOX4 itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4-plakoglobin interactions resulted in reduced transcriptional activity of β-catenin luciferase reporters. Conclusions These data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression.</p

A New Approach to Walking in Place

Abstract. Walking in Place (WIP) is an important locomotion technique used in virtual environments. This paper proposes a new approach to WIP, called Speed-Amplitude-Supported Walking-in-Place (SAS-WIP), which allows people, when walking along linear paths, to control their virtual speed based on footstep amplitude and speed metrics. We argue that our approach allows users to better control the virtual distance covered by the footsteps, achieve higher average speeds and experience less fatigue than when using state-of-the-art methods based on footstep frequency, called GUD-WIP. An in-depth user evaluation with twenty participants compared our approach to GUD-WIP on common travel tasks over a range of short, medium and long distances. We measured task performance using four distinct criteria: effectiveness, precision, efficiency and speed. The results show that SAS-WIP is both more efficient and faster than GUD-WIP when walking long distances while being more effective and precise over short distances. When asked their opinion via a post-test questionnaire, participants preferred SAS-WIP to GUD-WIP and reported experiencing less fatigue, having more fun and having a greater level of control when using our approach