Regulation of Na, K-ATPase Beta1-subunit In Cancer Cells

癌细胞中 Na、K-ATP 酶 Beta1 亚基的调节

• 批准号: 7494103
• 负责人: THU P HUYNH
• 金额: $ 1.24万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494103
• 关键词: Binding; Biological Assay; Cells; Development; Disease; Disseminated Malignant Neoplasm; E-Box Elements; E-Cadherin; Epithelial; Epithelial Cells; Event; Genetic Transcription; Glucocorticoid Receptor; Glucocorticoids; Homeostasis; Invasive; Ions; Laboratories; Malignant Epithelial Cell; Malignant Neoplasms; Mammalian Cell; Mesenchymal; Molecular; Na(+)-K(+)-Exchanging ATPase; Neoplasm Metastasis; Personal Satisfaction; Phenotype; Promoter Regions; Proteins; Pump; Regulation; Role; Snails; Sodium; Testing; Therapeutic; beta1 subunit Na K ATPase; cancer cell; cell motility; enzyme activity; epithelial to mesenchymal transition; human TACSTD1 protein; human TACSTD2 protein; insight; novel; potassium ion; small molecule; snail protein; tumor progression

DESCRIPTION (provided by applicant): Na,K-ATPase, consisting of a- and p-subunits, is a key regulator of sodium and potassium ion homeostasis in mammalian cells. In addition to its enzyme activity, the subunits are crucial to maintain the well- differentiated phenotype of epithelial cells. Reduced p-subunit expression is associated with epithelial mesenchymal transition (EMT) that occurs during cancer development. It has been shown that increased expression of the transcription suppressor protein, Snail, is elevated in invasive and metastatic cancer cells. We have previously demonstrated that the Na,K-ATPase prsubunit is suppressed by Snail in carcinoma cells. The first specific aim of this proposal examines the molecular mechanism by which Snail suppresses the transcription of Na,K-ATPase prsubunit. In the second aim, a novel assay will be employed to identify small molecules that might up-regulate Prsubunit expression in cancer cells. These studies should reveal insights into the role of pi-subunit in normal and cancer cells.

描述（由申请人提供）：Na,K-ATP酶由a-和p-亚基组成，是哺乳动物细胞中钠离子和钾离子稳态的关键调节剂。除了其酶活性外，这些亚基对于维持上皮细胞的良好分化表型也至关重要。 p 亚基表达减少与癌症发展过程中发生的上皮间质转化 (EMT) 相关。研究表明，转录抑制蛋白 Snail 的表达在侵袭性和转移性癌细胞中升高。我们之前已经证明，癌细胞中的 Na,K-ATP 酶亚基被 Snail 抑制。该提案的第一个具体目标是研究 Snail 抑制 Na,K-ATP 酶亚基转录的分子机制。第二个目标是采用一种新的检测方法来鉴定可能上调癌细胞中 Pr亚基表达的小分子。这些研究应该揭示 pi 亚基在正常细胞和癌细胞中的作用。