ROLE OF ANKYRIN COMPLEXES IN ANOIKIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 失巢凋亡的定义是被细胞外基质抑制的细胞凋亡；它是由我们的实验室发现的，并在1994年的《细胞生物学杂志》上发表了一篇论文。我们关注的是致癌EMT(上皮向间充质转化)使癌细胞对失巢凋亡产生抵抗的机制。特别是，我们正在研究ankyrins的作用，ankyrins是将肌动蛋白细胞骨架与包括E-钙粘附素在内的各种跨膜黏附受体连接的细胞骨架蛋白。我们假设，在正常的上皮细胞中，Ankyrin的表达建立了一个转录程序，允许细胞在细胞-基质分离的反应中死亡。相反，我们假设在癌细胞中频繁出现的锚蛋白的丢失建立了一个抗失巢凋亡的基因表达程序。这个项目解决了这些假设

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anoikis is defined as apoptosis that is inhibited by extracellular matrix; it was discovered by our laboratory and reported in a 1994 Journal of Cell Biology paper. We are focusing on the mechanisms by which the oncogenic EMT (epithelial-to-mesenchymal transition) confers resistance to anoikis upon carcinoma cells. In particular, we are investigating the role of ankyrins, cytoskeletal proteins that link the actin cytoskeleton to various transmembrane adhesion receptors including E-cadherin. We hypothesize that ankyrin expression in normal epithelial cells sets up a transcriptional program that permits cells to die in response to cell-matrix detachment. Conversely, we posit that the loss of ankyrin that occurs frequently in carcinoma cells establishes an anoikis-resistance gene expression program. This project addresses these hypotheses