Crosstalk between WNT and Hippo signaling pathways is affected by cell density and loss of or mutated E-cadherin protein, associated to HDGC.

摘要: A cell that senses signals from its environment uses proteins for signal transduction via post translational modifications (PTMs) and protein- protein interactions (PPIs) membrane into the nucleus where genes controlling proliferation, differentiation apoptosis can be turned on or off, i.e. changing phenotype fate of cell. Aberrations within such are prone to cause diseases, as cancer. Therefore, it is important so study aberrant signaling able understand treat diseases.In this thesis, aberrations PTMs PPIs were analyzed with use in situ proximity ligation assay (in PLA), thesis also contain method development rolling circle amplification (RCA), which used PLA reaction products.Paper I considers integrity RCA products. Here, aim was generate a smaller more compact product, accurate either visual automated analysis. This achieved an additional called compaction oligonucleotide during bind pull segments products closer together. The served increase noise ratio decrease number false positive signals.The crosstalk between Hippo TGFβ pathways studied paper II. Activity pathway regulated by density sensing tissue control. We found differences amounts localization effector two depending stimulation.In III NF-кB constitutively activated chronic lymphocytic leukemia (CLL) studied. 4 base-pair frameshift deletion NFKBIE gene, encodes negative regulator IкBe, among 13 total 315 cases targeted deep sequencing. reduced levels IкBe protein, decreased p65 inhibition, increased phosphorylation, along nuclear deleted compared healthy cases.Crosstalk Wnt IV. we cellular TAZ/β-catenin colon cancer tumor stage further investigate Hippo/WNT line model systems complex formations involved sparse growing HEK293 cells dense cells. Also, active WNT3a affected density. Since showed have big effect continued investigated E-cadherin, has function junctions maintenance epithelial crosstalk. Interestingly, E-cadherin likely regulate