Epithelia are active materials where mechanical tension governs morphogenesis and homeostasis. But how that tension is regulated remains incompletely understood. We now report that caveolae control epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion. Depletion of caveolin-1 (CAV1) increased steady-state tensile stresses in epithelial monolayers. As a result, loss of CAV1 in the epithelial cells surrounding oncogene-expressing cells prevented their apical extrusion. Epithelial tension in CAV1-depleted monolayers was increased by cortical contractility at adherens junctions. This reflected a signaling pathway, where elevated levels of phosphoinositide-4,5-bisphosphate (PtdIns(4,5)P₂) recruited the formin, FMNL2, to promote F-actin bundling. Steady-state monolayer tension and oncogenic extrusion were restored to CAV1-depleted monolayers when tension was corrected by depleting FMNL2, blocking PtdIns(4,5)P₂, or disabling the interaction between FMNL2 and PtdIns(4,5)P₂. Thus, caveolae can regulate active mechanical tension for epithelial homeostasis by controlling lipid signaling to the actin cytoskeleton.

上皮细胞是机械张力控制形态发生和体内平衡的活性物质。但是，如何调节这种张力仍未完全理解。现在，我们报告小窝控制上皮张力，并表明这对于通过根尖挤压消除癌基因转染的细胞是必要的。Caveolin-1（CAV1）的消耗增加了上皮单层的稳态拉伸应力。结果，表达癌基因的细胞周围的上皮细胞中CAV1的丢失阻止了它们的顶端挤出。CAV1耗尽的单层中的上皮张力因粘附连接处的皮质收缩而增加。这反映了信号通路，其中磷酸肌醇4,5-双磷酸（PtdIns（4,5）P ₂）招募了FORMNL FMNL2，以促进F-肌动蛋白捆绑。当通过消耗FMNL2，阻止PtdIns（4,5）P ₂或禁用FMNL2和PtdIns（4,5）P ₂的相互作用来校正张力时，稳态单层张力和致癌性挤出恢复为CAV1耗尽的单层。因此，小窝可以通过控制向肌动蛋白细胞骨架的脂质信号传导来调节上皮稳态的主动机械张力。