Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that modulation of Ras/MAPK or TGFb signaling drive BST. Here, we induce Ras/MAPK and/or abrogate TGFb signaling to induce BST. Alternatively we drive c-FOS to induce BST. In these various experimentally-induced model of BST, we analyze chromatin accessibility profiles upon Ras/MAPK activation and/or TGFb signaling abrogation. We also analyze chromatin accessibility profiles upon c-FOS activation.
Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that modulation of Ras/MAPK or TGFb signaling drive BST. Here, we induce Ras/MAPK and/or abrogate TGFb signaling to induce BST. Alternatively we drive c-FOS to induce BST. Here, we analyze transcriptional profiles upon c-FOS induction.
Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that modulation of Ras/MAPK or TGFb signaling drive BST. Here, we induce Ras/MAPK and/or abrogate TGFb signaling to induce BST. Alternatively we drive c-FOS to induce BST. Here, we analyze transcriptional profiles upon Ras/MAPK activation and/or TGFb signaling abrogation.
Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that modulation of Ras/MAPK or TGFb signaling drive BST. Here, we induce Ras/MAPK and/or abrogate TGFb signaling to induce BST. Alternatively we drive c-FOS to induce BST. Here, we analyze chromatin accessibility profiles upon c-FOS activation
Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that modulation of Ras/MAPK or TGFb signaling drive BST. Here, we induce Ras/MAPK and/or abrogate TGFb signaling to induce BST and examine the DNA binding profile of the AP-1 transcription factor c-FOS.
Project description:Basal cell carcinoma may undergo BST spontaneously or upon Hedgehog targeting therapy. We identified that either modulation of Ras/MAPK or TGFb signaling or c-FOS induction could drive BST. Enhanced EGFR signaling has been implicated during BST. Here, we analyze transcriptional profiles upon c-FOS induction when cells are treated with EGFR signaling inhibitors afatinib (5uM) and UO126 (10uM).
Project description:Neocarzilin (NCA) is a natural product exhibiting potent anti-migratory as well as anti-proliferative effects. While the vesicle amide transport protein 1 (VAT-1) was previously shown to inhibit migration upon NCA binding, the molecular mechanisms responsible for impaired proliferation remained elusive. We here introduce a chemical probe closely resembling the structural and stereochemical features of NCA and unravel bone marrow stromal antigen 2 (BST-2) as a second major target in cancer cells. The antiproliferative mechanism of NCA was confirmed in corresponding BST-2 knockout (KO) cells which were less sensitive to compound treatment. Vice versa, overexpression of the target in the KO reduced proliferation comparable to wild type (wt) cells. Whole proteome mass-spectrometric (MS) analysis of NCA treated wt and KO cancer cells unraveled affected pathways linked to EGFR signaling and demonstrated reduced levels of BST-2 upon NCA treatment. In-depth analysis of BST-2 levels in response to proteasome and lysosome inhibitors, confirmed a lysosomal degradation path upon NCA treatment. As BST-2 is mediating the release of EGFR from lipid rafts to turn on proliferation signaling pathways, reduced BST-2 levels led to attenuated phosphorylation of EGFR and downstream targets. Furthermore, fluorescence microscopy confirmed colocalization of BST-2 and lipid rafts in presence of NCA. Overall, NCA represents a versatile anti-cancer natural product with a unique dual mode of action and unconventional inhibition of proliferation via BST-2 degradation.
Project description:We sought to understand the change in the global gene expression profile of the ΔYGP1 strain in comparison with the BGL-6_Kl parental strain. The transcriptome analysis revealed the change in expression of genes involved in cell wall structure, biogenesis, and integrity that might contribute to the improvement of the BGL display efficiency phenotype.