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

转化生长因子β (tgf - β)通过多种环境依赖的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复归，以及其他作用。tgf - β信号通过典型（Smad）和非典型途径（如Par6和PI3K/Akt）传递，这两种途径都促进了对tgf - β的最佳记录细胞反应之一：上皮-间质转化（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）和顶基极性的丧失。我们发现，在正常乳腺细胞响应TGFβ进行EMT时，细胞凋亡与紧密连接和顶基极性的破坏并行发生，并增强细胞外囊泡的释放。Par6通过调节PI3K/Akt/FoxO信号通路以及其他信号通路介导这些过程。我们

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