TY - GEN A1 - Pastro, Lucia A1 - Martínez, Jennyfer A1 - Fontenla, Santiago A1 - Chiale, Ana C. A1 - Faulord, Agustina A1 - Frade, María P. A1 - Díaz, Andrea S. A1 - Martino-Kunsch, Rodrigo A1 - Castro, Laura A1 - Schenk, Lysann A1 - Quijano, Celia A1 - Sturge, Justin A1 - Rodríguez-Teja, Mercedes T1 - Endo180 and basement membrane stiffness induce OXPHOS and neoplastic transformation in aging prostate epithelia T2 - npj aging N2 - During prostate aging collagen-IV is modified by advanced glycation end-products, inducing crosslinking of the basement membrane surrounding glandular acini. Basement membrane stiffness sensed by Endo180 disrupts its suppressor complex with CD147, triggering epithelial-to-mesenchymal transition and limiting survival in prostate cancer patients. Here we report basement membrane stiffness and Endo180 cooperate in rewiring epithelia for mitochondrial oxidative phosphorylation (OXPHOS) and growth suppressor evasion, cell proliferation promotion, cell death resistance, inflammation, invasion and metastasis without affecting genome instability, highlighting a non-oncogenic biomechanical event in age-related neoplasia. Endo180-CD147 complex coupled to OXPHOS in Gleason 6 and in Gleason ≥7 tumors Endo180 uncoupled from CD147-OXPHOS, identifying a bio-switch for invasive cancer. Endo180 correlated with patient age in normal tissue, Gleason 6 and 7, but not Gleason 8 tumors, suggesting biological age unleashes its suppression of tumorigenesis. Application of Endo180-based diagnostics in age-related glandular cancers could inform treatment decisions, improving quality of life and survival. Y1 - 2025 U6 - https://doi.org/10.1038/s41514-025-00259-4 SN - 2731-6068 VL - 11 IS - 1 SP - 1 EP - 15 PB - Nature Publishing Group UK CY - London ER - TY - GEN A1 - Liedtke, Victoria A1 - Weiss, Romano A1 - Skifov, Anastasia A1 - Rödiger, Stefan A1 - Schenk, Lysann T1 - Fully automated viability and toxicity screening - areliable all‐in‐one attempt T2 - Cancer Medicine N2 - The CRISPR/Cas9 technology is nowadays a common tool for genome editing to achieve new insights into, for example, diagnostics and therapeutics in cancer and genetic disorders. Cell proliferation and anticancer drug response studies are widely used to evaluate the impact of editing. However, these assays are often time‐consuming, expensive, and reproducibility is an issue. To overcome this, we developed a fast and cheap assay that combines a fully automated multispectral fluorescence microscopy platform with a nuclei staining and open‐source software analysis.Here, we generated different LEDGF/p75 model cell lines to validate the effect on proliferation and chemosensitivity. Therefore, a fast protocol for an optimized all‐in‐one attempt for cytotoxicity screenings and proliferation analysis of adherent cells in a 96‐well plate format was established using differential staining with two fluorescent dyes (Hoechst 33342 and propidium iodide) for live/dead cell discrimination. Subsequently, an automated cell nuclei count and analysis were performed using bioimage informatics.With the new established assay technology, up to 50,000 cells/well can be detected and analyzed in a 96‐well plate, resulting in a fast and accurate verification of viability and proliferation with consistency of 98% compared to manual counting. Our screening revealed that LEDGF depletion using CRISPR/Cas9 showed a diminished proliferation and chemosensitivity independent of cell line origin. Moreover, LEDGF depletion caused a significant increase in 𝛾H2AX foci, indicating a substantial increase in DNA double strand breaks. LEDGF/p75 overexpression enhanced proliferation and chemoresistance underlining the role of LEDGF in DNA damage response.Independent of cancer cell type, LEDGF/p75 is a central player in DNA damage repair and is implicated in chemoresistance. Moreover, our automated fluorescence biosensor technology allowed fast and reliable data acquisition without any fixation or additional washing steps. Additionally, data analysis was implemented using the modular open‐source software that can be adapted as needed. Y1 - 2024 U6 - https://doi.org/10.1002/cam4.7392 SN - 2045-7634 VL - 13 IS - 12 PB - Wiley ER - TY - GEN A1 - Liedtke, Victoria A1 - Stöckle, Michael A1 - Junker, Kerstin A1 - Roggenbuck, Dirk T1 - Benign prostatic hyperplasia - a novel autoimmune disease with a potential therapy consequence? T2 - Autoimmunity Reviews N2 - Benign prostatic hyperplasia (BPH) is considered as an age-related disease of men with an unknown etiopathophysiology. Chronic inflammation has been proposed as one of the major pathophysiological mechanisms. There is growing evidence for the involvement of autoimmune responses in an inflammatory setting in the prostate. Patients with autoimmune diseases show a significantly elevated prevalence of BPH. Conventional therapy options for BPH are limited, rendering surgery the ultimate alternative. However, immunosuppression via tumor necrosis factor alpha blocker appears to reduce symptoms in patients with BPH and concurrent autoimmune disease due to the reduction of epithelial hyperplasia and macrophage-induced inflammation. New diagnostic options using HEp-2 cells with overexpression of LEDGF/p75 or mitochondrial DNA as autoimmune targets could be used to identify BPH patients with autoimmune responses. Given the presumed involvement of autoimmune responses in BPH and the efficacy of immunosuppression in reducing BPH symptoms, BPH or subvariants of BPH may be candidates for a new autoimmune disease in males. KW - Autoimmunity Benign prostatic hyperplasia Anti-mitochondrial DNA antibodies LEDGF/p75 Y1 - 2024 U6 - https://doi.org/10.1016/j.autrev.2023.103511 SN - 1568-9972 VL - 23 IS - 3 PB - Elsevier BV ER - TY - GEN A1 - Liedtke, Victoria A1 - Schröder, Christian A1 - Roggenbuck, Dirk A1 - Weiss, Romano A1 - Stohwasser, Ralf A1 - Schierack, Peter A1 - Rödiger, Stefan A1 - Schenk, Lysann T1 - LEDGF/p75 is required for an efficient DNA damage response T2 - International Journal of Molecular Sciences KW - LEDGF KW - CRISPR/Cas9 KW - DNA damage signaling KW - gH2AX KW - ubiquitination Y1 - 2021 U6 - https://doi.org/10.3390/ijms22115866 VL - 22 IS - 11 SP - 1 EP - 16 ER -