Linking junctional integrity and cell polarity to TGF-beta function in the normal mammary gland

将正常乳腺中的连接完整性和细胞极性与 TGF-β 功能联系起来

• 批准号: RGPIN-2017-03977
• 负责人: ViloriaPetit, Alicia
• 金额: $ 1.89万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629333
• 关键词: Linking; junctional; integrity; cell; polarity

Transforming growth factor beta (TGFβ) mediates epithelial homeostasis via a number of context-dependent cellular effects, including cell death/apoptosis, growth arrest, survival, and motility. For instance, TGFβ mediates mammary gland morphogenesis as a growth inhibitor, and post-lactation involution as an apoptosis inducer, among other effects. TGFβ signals via canonical (Smad) and non-canonical pathways (e.g. Par6 and PI3K/Akt), both of which facilitate one of the best-documented cellular responses to TGFβ: the epithelial-mesenchymal transition (EMT). A key feature of EMT is the loss of cell-cell junctions (tight and adherens junctions) and apical-basal polarity. We found that in normal mammary cells undergoing EMT in response to TGFβ, apoptosis occurs in parallel to the disruption of tight junctions and apical-basal polarity, and an enhanced release of extracellular vesicles. Par6 mediates these processes in association with modulation of PI3K/Akt/FoxO signalling, as well as other signalling pathways. We

转化生长因子β（TGFβ）通过许多环境依赖性细胞效应介导上皮稳态，包括细胞死亡/凋亡、生长停滞、存活和运动。例如，TGFβ作为生长抑制剂介导乳腺形态发生，作为细胞凋亡诱导剂介导泌乳后退化，以及其他作用。TGFβ通过经典（Smad）和非经典途径（例如Par 6和PI 3 K/Akt）进行信号传导，这两种途径都促进了对TGFβ的最佳记录的细胞应答之一：上皮-间充质转化（EMT）。EMT的一个关键特征是细胞-细胞连接（紧密连接和粘附连接）和顶端-基底极性的丧失。我们发现，在正常乳腺细胞中，由于TGFβ的作用而发生EMT，细胞凋亡的发生与紧密连接和顶端-基底极性的破坏以及细胞外囊泡释放的增强平行。Par 6介导这些过程与PI 3 K/Akt/FoxO信号传导以及其他信号传导途径的调节相关。我们